Skip to main content
SpringerLink
Log in

Analyzing the Function of Tumor Suppressor Genes Using a Drosophila Model

  • Protocol
Tumor Suppressor Genes

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 223))

Abstract

With 1600 eyes, a pair of antennae, 6 legs, and an open circulatory system, the fruit fly Drosophila melanogaster may seem an unlikely model for the host of pathologies resulting from human cancers. However, the results of a century of research in Drosophila only accents the fundamental similarities between many biologic processes in both flies and humans. And as genetic analysis in yeast lent crucial insights into the conserved mechanisms of cell division and cell cycle control (1,2), genetic studies in a relatively simple multicellular organism such as Drosophila can help us understand how mutations in tumor suppressor genes and oncogenes affect organs and tissues, and also help us to find new genes functioning in the processes related to cancer biology. The goal of this chapter is to review how one can use Drosophila as a model to study the functions of tumor suppressor or oncogene homologs, and to identify novel genes involved in tumorigenic processes. We discuss why Drosophila is a relevant model for cancer development in mammals, and why studies in Drosophila offer advantages over a number of other model systems. We review the history of studying cancer in Drosophila, and explain the powerful genetic techniques that allow for refined in-vivo studies of cancer-causing genes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Russell, P. (1998) Checkpoints on the road to mitosis. Trends Biochem. Sci. 23, 399–402.

    PubMed  CAS  Google Scholar 

  2. Wassmann, K. and Benezra, R. (2001) Mitotic checkpoints: from yeast to cancer. Curr. Opin. Genet. Dev. 11, 83–90.

    PubMed  CAS  Google Scholar 

  3. Rubin, G. M., Yandell, M. D., Wortman, J. R., et al. (2000) Comparative genomics of the eukaryotes. Science 287, 2204–2215.

    PubMed  CAS  Google Scholar 

  4. Hahn, H., Wojnowski, L., Miller, G., and Zimmer, A. (1999) The patched signaling pathway in tumorigenesis and development: lessons from animal models. J. Mol. Med. 77, 459–468.

    PubMed  CAS  Google Scholar 

  5. Booth, D. R. (1999) The hedgehog signalling pathway and its role in basal cell carcinoma. Cancer Metastasis Rev. 18, 261–284.

    PubMed  CAS  Google Scholar 

  6. Siegfried, E. and Perrimon, N. (1994) Drosophila wingless: a paradigm for the function and mechanism of Wnt signaling. Bioessays 16, 395–404.

    PubMed  CAS  Google Scholar 

  7. Hahn, H., Wicking, C., Zaphiropoulous, P. G., et al. (1996) Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85, 841–851.

    PubMed  CAS  Google Scholar 

  8. Nusslein-Volhard, C., Wieschaus, E., and Kluding, H. (1984) Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster. Roux’s Arch. Dev. Biol. 193, 267–282.

    Google Scholar 

  9. Vidwans, S. J. and Su, T. T. (2001) Cycling through development in Drosophila and other metazoa. Nat. Cell Biol. 3, E35–E39.

    PubMed  CAS  Google Scholar 

  10. Edgar, B. A. and Lehner, C. F. (1996) Developmental control of cell cycle regulators: a fly’s perspective. Science 274, 1646–1652.

    PubMed  CAS  Google Scholar 

  11. Orr-Weaver, T. L. (1994) Developmental modification of the Drosophila cell cycle. Trends Genet. 10, 321–327.

    PubMed  CAS  Google Scholar 

  12. Oldham, S., Bohni, R., Stocker, H., Brogiolo, W., and Hafen, E. (2000) Genetic control of size in Drosophila. Phil. Trans. R. Soc. Lond. B, Biol. Sci. 355, 945–952.

    CAS  Google Scholar 

  13. Stocker, H. and Hafen, E. (2000) Genetic control of cell size. Curr. Opin. Genet. Dev. 10, 529–535.

    PubMed  CAS  Google Scholar 

  14. Potter, C. J. and Xu, T. (2001) Mechanisms of size control. Curr. Opin. Genet. Dev. 11, 279–286.

    PubMed  CAS  Google Scholar 

  15. Sekelsky, J. J., Brodsky, M. H., and Burtis, K. C. (2000) DNA repair in Drosophila: insights from the Drosophila genome sequence. J. Cell Biol. 150, F31–F36.

    PubMed  CAS  Google Scholar 

  16. Abrams, J. M. (1999) An emerging blueprint for apoptosis in Drosophila. Trends Cell Biol. 9, 435–440.

    PubMed  CAS  Google Scholar 

  17. Steller, H., Abrams, J. M., Grether, M. E., and White, K. (1994) Programmed cell death in Drosophila. Phil. Trans. R. Soc. Lond. B, Biol. Sci. 345, 247–250.

    CAS  Google Scholar 

  18. Vernooy, S. Y., Copeland, J., Ghaboosi, N., Griffin, E. E., Yoo, S. J., and Hay, B. A. (2000) Cell death regulation in Drosophila: conservation of mechanism and unique insights. J. Cell Biol. 150, F69–F76.

    PubMed  CAS  Google Scholar 

  19. Meier, P., Finch, A., and Evan, G. (2000) Apoptosis in development. Nature 407, 796–801.

    PubMed  CAS  Google Scholar 

  20. Lee, C. Y. and Baehrecke, E. H. (2000) Genetic regulation of programmed cell death in Drosophila. Cell Res. 10, 193–204.

    PubMed  CAS  Google Scholar 

  21. Bangs, P. and White, K. (2000) Regulation and execution of apoptosis during Drosophila development. Dev. Dyn. 218, 68–79.

    PubMed  CAS  Google Scholar 

  22. Joutel, A. and Tournier-Lasserve, E. (1998) Notch signalling pathway and human diseases. Semin. Cell Dev. Biol. 9, 619–625.

    PubMed  CAS  Google Scholar 

  23. Cohen, S. M. (1993) Imaginal disc development, in The Development of Drosophila Melanogaster (Bate, M., and Martinez Arias, A., eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N Y, vol. 2, pp. 747–842.

    Google Scholar 

  24. Bryant, P. J. and Schmidt, O. (1990) The genetic control of cell proliferation in Drosophila imaginal discs. J. Cell Sci. Suppl. 13, 169–189.

    PubMed  CAS  Google Scholar 

  25. Capdevila, J. and Johnson, R. L. (2000) Hedgehog signaling in vertebrate and invertebrate limb patterning. Cell. Mol. Life Sci. 57, 1682–1694.

    PubMed  CAS  Google Scholar 

  26. Gehring, W. J. (1996) The master control gene for morphogenesis and evolution of the eye. Genes Cells 1, 11–15.

    PubMed  CAS  Google Scholar 

  27. Chen, J. N. and Fishman, M. C. (2000) Genetics of heart development. Trends Genet. 16, 383–388.

    PubMed  CAS  Google Scholar 

  28. Myers, E. W., Sutton, G. G., Delcher, A. L., et al. (2000) A whole-genome assembly of Drosophila. Science 287, 2196–2204.

    PubMed  CAS  Google Scholar 

  29. Adams, M. D., Celniker, S. E., Holt, R. A., et al. (2000) The genome sequence of Drosophila melanogaster. Science 287, 2185–2195.

    PubMed  Google Scholar 

  30. Ashburner, M. (1989) Chromosomes, in Drosophila—A Laboratory Manual (Ashburner, M., ed.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, vol. 2, pp. 21–72.

    Google Scholar 

  31. Ashburner, M. (1989) Balancers and other special chromosomes, in Drosophila—A Laboratory Manual (Ashburner, M., ed.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, vol. 2, pp. 529–548.

    Google Scholar 

  32. Huang, A. M., Rehm, E. J., and Rubin, G. M. (2000) Recovery of DNA sequences flanking P-element insertions: inverse PCR and plasmid rescue, in Drosophila Protocols (Sullivan, W., Ashburner, M., and Hawley, R. S., eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 429–438.

    Google Scholar 

  33. Spradling, A. C. (1986) P-element mediated transformation, in Drosophila: A Practical Approach (Roberts, D., ed.). IRL Press, Oxford, UK, pp. 175–198.

    Google Scholar 

  34. Stark, M. B. (1918) An hereditary tumor in Drosophila. J. Cancer Res. 3, 279–301.

    Google Scholar 

  35. Gateff, E. (1978) Malignant neoplasms of genetic origin in Drosophila melanogaster. Science 200, 1448–1459.

    PubMed  CAS  Google Scholar 

  36. Gateff, E. and Schneiderman, H. A. (1969) Neoplasms in mutant and cultured wild-type tissues of Drosophila. Natl. Cancer Inst. Monogr. 31, 365–397.

    PubMed  CAS  Google Scholar 

  37. Watson, K. L., Justice, R. W., and Bryant, P. J. (1994) Drosophila in cancer research: the first fifty tumor suppressor genes. J. Cell Sci. Suppl. 18, 19–33.

    PubMed  CAS  Google Scholar 

  38. Gateff, E. and Mechler, B. M. (1989) Tumor-suppressor genes of Drosophila melanogaster. Crit. Rev. Oncog. 1, 221–245.

    PubMed  CAS  Google Scholar 

  39. Xu, T., Wang, W., Zhang, S., Stewart, R. A., and Yu, W. (1995) Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 121, 1053–1063.

    PubMed  CAS  Google Scholar 

  40. Tao, W., Zhang, S., Turenchalk, G. S., et al. (1999) Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. Nat. Genet. 21, 177–181.

    PubMed  CAS  Google Scholar 

  41. St John, M. A., Tao, W., Fei, X., et al. (1999) Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nat. Genet. 21, 182–186.

    PubMed  CAS  Google Scholar 

  42. Waltzer, L. and Bienz, M. (1999) The control of beta-catenin and TCF during embryonic development and cancer. Cancer Metastasis Rev. 18, 231–246.

    PubMed  CAS  Google Scholar 

  43. Huang, H., Potter, C. J., Tao, W., et al. (1999) PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development 126, 5365–5372.

    PubMed  CAS  Google Scholar 

  44. Tapon, N., Ito, N., Dickson, B. J., Treisman, J. E., and Hariharan, I. K. (2001) The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 105, 345–355.

    PubMed  CAS  Google Scholar 

  45. Potter, C. J., Huang, H., and Xu, T. (2001) Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105, 357–368.

    PubMed  CAS  Google Scholar 

  46. Gao, X., Neufeld, T. P., and Pan, D. (2000) Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and-independent pathways. Dev. Biol. 221, 404–418.

    PubMed  CAS  Google Scholar 

  47. Gao, X. and Pan, D. (2001) TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 15, 1383–1392.

    PubMed  CAS  Google Scholar 

  48. Goberdhan, D. C., Paricio, N., Goodman, E. C., Mlodzik, M., and Wilson, C. (1999) Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes Dev. 13, 3244–3258.

    PubMed  CAS  Google Scholar 

  49. Ashburner, M. (1989) Mutation and mutagenesis, in Drosophila—A Laboratory Handbook (Ashburner, M., ed.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N Y, vol. 2, pp. 299–418.

    Google Scholar 

  50. Cooley, L., Kelley, R., and Spradling, A. (1988) Insertional mutagenesis of the Drosophila genome with single P elements. Science 239, 1121–1128.

    PubMed  CAS  Google Scholar 

  51. Spradling, A. C., Stern, D. M., Kiss, I., Roote, J., Laverty, T., and Rubin, G. M. (1995) Gene disruptions using P transposable elements: an integral component of the Drosophila genome project. Proc. Natl. Acad. Sci. USA 92, 10824–10830.

    PubMed  CAS  Google Scholar 

  52. Xu, T. and Rubin, G. M. (1993) Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117, 1223–1237.

    PubMed  CAS  Google Scholar 

  53. Xu, T. and Harrison, S. D. (1994) Mosaic analysis using FLP recombinase. Meth. Cell Biol. 44, 655–681.

    CAS  Google Scholar 

  54. Golic, K. G. (1991) Site-specific recombination between homologous chromosomes in Drosophila. Science 252, 958–961.

    PubMed  CAS  Google Scholar 

  55. Geyer, P. K., Richardson, K. L., Corces, V. G., and Green, M. M. (1988) Genetic instability in Drosophila melanogaster: P-element mutagenesis by gene conversion. Proc. Natl. Acad. Sci. USA 85, 6455–6459.

    PubMed  CAS  Google Scholar 

  56. Margulies, L. and Griffith, C. S. (1991) The synergistic effect of X-rays and deficiencies in DNA repair in P-M hybrid dysgenesis in Drosophila melanogaster. Genet. Res. 58, 15–26.

    PubMed  CAS  Google Scholar 

  57. Chen, B., Chu, T., Harms, E., Gergen, J. P., and Strickland, S. (1998) Mapping of Drosophila mutations using site-specific male recombination. Genetics 149, 157–163.

    PubMed  CAS  Google Scholar 

  58. Golic, K. G. (1994) Local transposition of P elements in Drosophila melanogaster and recombination between duplicated elements using a site-specific recombinase. Genetics 137, 551–563.

    PubMed  CAS  Google Scholar 

  59. Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., and Mello, C. C. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans [see comments]. Nature 391, 806–811.

    PubMed  CAS  Google Scholar 

  60. Kennerdell, J. R. and Carthew, R. W. (1998) Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell 95, 1017–1026.

    PubMed  CAS  Google Scholar 

  61. Misquitta, L. and Paterson, B. M. (1999) Targeted disruption of gene function in Drosophila by RNA interference (RNA-i): a role for nautilus in embryonic somatic muscle formation. Proc. Natl. Acad. Sci. USA 96, 1451–1456.

    PubMed  CAS  Google Scholar 

  62. Caplen, N. J., Fleenor, J., Fire, A., and Morgan, R. A. (2000) dsRNA-mediated gene silencing in cultured Drosophila cells: a tissue culture model for the analysis of RNA interference. Gene 252, 95–105.

    PubMed  CAS  Google Scholar 

  63. Kennerdell, J. R. and Carthew, R. W. (2000) Heritable gene silencing in Drosophila using double-stranded RNA. Nat. Biotechnol. 18, 896–898.

    PubMed  CAS  Google Scholar 

  64. Rong, Y. S. and Golic, K. G. (2000) Gene targeting by homologous recombination in Drosophila. Science 288, 2013–2018.

    PubMed  CAS  Google Scholar 

  65. Rong, Y. S. and Golic, K. G. (2001) A targeted gene knockout in Drosophila. Genetics 157, 1307–1312.

    PubMed  CAS  Google Scholar 

  66. Hama, C., Ali, Z., and Kornberg, T. B. (1990) Region-specific recombination and expression are directed by portions of the Drosophila engrailed promoter. Genes Dev. 4, 1079–1093.

    PubMed  CAS  Google Scholar 

  67. Hauck, B., Gehring, W. J., and Walldorf, U. (1999) Functional analysis of an eye specific enhancer of the eyeless gene in Drosophila. Proc. Natl. Acad. Sci. USA 96, 564–569.

    PubMed  CAS  Google Scholar 

  68. Kim, Y. J. and Baker, B. S. (1993) The Drosophila gene rbp9 encodes a protein that is a member of a conserved group of putative RNA binding proteins that are nervous systemspecific in both flies and humans. J. Neurosci. 13, 1045–1056.

    PubMed  CAS  Google Scholar 

  69. Bonner, J. J., Parks, C., Parker-Thornburg, J., Mortin, M. A., and Pelham, H. R. (1984) The use of promoter fusions in Drosophila genetics: isolation of mutations affecting the heat shock response. Cell 37, 979–991.

    PubMed  CAS  Google Scholar 

  70. Brand, A. H. and Perrimon, N. (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415.

    PubMed  CAS  Google Scholar 

  71. Rorth, P., Szabo, K., Bailey, A., et al. (1998) Systematic gain-of-function genetics in Drosophila. Development 125, 1049–1057.

    PubMed  CAS  Google Scholar 

  72. Struhl, G. and Basler, K. (1993) Organizing activity of wingless protein in Drosophila. Cell 72, 527–540.

    PubMed  CAS  Google Scholar 

  73. St John, M. A. and Xu, T. (1997) Understanding human cancer in a fly? Am. J. Hum. Genet. 61, 1006–1010.

    PubMed  CAS  Google Scholar 

  74. Lee, T. and Luo, L. (2001) Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development. Trends Neurosci. 24, 251–254.

    PubMed  CAS  Google Scholar 

  75. Lee, T. and Luo, L. (1999) Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron 22, 451–461.

    PubMed  CAS  Google Scholar 

  76. Neufeld, T. P., de la Cruz, A. F., Johnston, L. A., and Edgar, B. A. (1998) Coordination of growth and cell division in the Drosophila wing. Cell 93, 1183–1193.

    PubMed  CAS  Google Scholar 

  77. Morata, G. and Ripoll, P. (1975) Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev. Biol. 42, 211–221.

    PubMed  CAS  Google Scholar 

  78. Chou, T. B. and Perrimon, N. (1996) The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster. Genetics 144, 1673–1679.

    PubMed  CAS  Google Scholar 

  79. Stowers, R. S. and Schwarz, T. L. (1999) A genetic method for generating Drosophila eyes composed exclusively of mitotic clones of a single genotype. Genetics 152, 1631–1639.

    PubMed  CAS  Google Scholar 

  80. Foe, V. E., Odell, G. M., and Edgar, B. A. (1993) Mitosis and morphogenesis in the Drosophila embryo: point and counterpoint, in The Development of Drosophila Melanogaster (Bate, M., and Martinez Arias, A., eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N Y, vol. 1, pp. 149–300.

    Google Scholar 

  81. Su, T. T., Campbell, S. D., and O’Farrell, P. H. (1999) Drosophila grapes/CHK1 mutants are defective in cyclin proteolysis and coordination of mitotic events. Curr. Biol. 9, 919–922.

    PubMed  CAS  Google Scholar 

  82. Grosshans, J. and Wieschaus, E. (2000) A genetic link between morphogenesis and cell division during formation of the ventral furrow in Drosophila. Cell 101, 523–531.

    PubMed  CAS  Google Scholar 

  83. Hazelrigg, T. (2000) GFP and other reporters, in Drosophila Protocols (Sullivan, W., Ashburner, M., and Hawley, R. S., eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 313–344.

    Google Scholar 

  84. Wolff, T. (2000) Histological techniques for the Drosophila eye. Part I: larva and pupa, in Drosophila Protocols (Sullivan, W., Ashburner, M., and Hawley, R. S., eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 201–228.

    Google Scholar 

  85. Blair, S. S. (2000) Imaginal discs, in Drosophila Protocols (Sullivan, W., Ashburner, M., and Hawley, R. S., eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 159–174.

    Google Scholar 

  86. Woods, D. F., Wu, J. W., and Bryant, P. J. (1997) Localization of proteins to the apico-lateral junctions of Drosophila epithelia. Dev. Genet. 20, 111–118.

    PubMed  CAS  Google Scholar 

  87. Garoia, F., Guerra, D., Pezzoli, M. C., Lopez-Varea, A., Cavicchi, S., and Garcia-Bellido, A. (2000) Cell behaviour of Drosophila fat cadherin mutations in wing development. Mech. Dev. 94, 95–109.

    PubMed  CAS  Google Scholar 

  88. Mahoney, P. A., Weber, U., Onofrechuk, P., Biessmann, H., Bryant, P. J., and Goodman, C. S. (1991) The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily. Cell 67, 853–868.

    PubMed  CAS  Google Scholar 

  89. Bryant, P. J., Huettner, B., Held, L. I., Jr., Ryerse, J., and Szidonya, J. (1988) Mutations at the fat locus interfere with cell proliferation control and epithelial morphogenesis in Drosophila. Dev. Biol. 129, 541–554.

    PubMed  CAS  Google Scholar 

  90. Boedigheimer, M. J., Nguyen, K. P., and Bryant, P. J. (1997) Expanded functions in the apical cell domain to regulate the growth rate of imaginal discs. Dev. Genet. 20, 103–110.

    PubMed  CAS  Google Scholar 

  91. Boedigheimer, M. and Laughon, A. (1993) Expanded: a gene involved in the control of cell proliferation in imaginal discs. Development 118, 1291–1301.

    PubMed  CAS  Google Scholar 

  92. Blaumueller, C. M. and Mlodzik, M. (2000) The Drosophila tumor suppressor expanded regulates growth, apoptosis, and patterning during development. Mech. Dev. 92, 251–262.

    PubMed  CAS  Google Scholar 

  93. Jursnich, V. A., Fraser, S. E., Held, L. I., Jr., Ryerse, J., and Bryant, P. J. (1990) Defective gap-junctional communication associated with imaginal disc overgrowth and degeneration caused by mutations of the dco gene in Drosophila. Dev. Biol. 140, 413–429.

    PubMed  CAS  Google Scholar 

  94. Woodhouse, E., Hersperger, E., and Shearn, A. (1998) Growth, metastasis, and invasiveness of Drosophila tumors caused by mutations in specific tumor suppressor genes. Dev. Genes Evol. 207, 542–550.

    PubMed  CAS  Google Scholar 

  95. Woodhouse, E., Hersperger, E., Stetler-Stevenson, W. G., Liotta, L. A., and Shearn, A. (1994) Increased type IV collagenase in lgl-induced invasive tumors of Drosophila. Cell Growth Differ. 5, 151–159.

    PubMed  CAS  Google Scholar 

  96. Strand, D., Jakobs, R., Merdes, G., et al. (1994) The Drosophila lethal(2)giant larvae tumor suppressor protein forms homo-oligomers and is associated with nonmuscle myosin II heavy chain. J. Cell Biol. 127, 1361–1373.

    PubMed  CAS  Google Scholar 

  97. Mechler, B. M., McGinnis, W., and Gehring, W. J. (1985) Molecular cloning of lethal(2)giant larvae, a recessive oncogene of Drosophila melanogaster. EMBO J. 4, 1551–1557.

    PubMed  CAS  Google Scholar 

  98. Woods, D. F. and Bryant, P. J. (1989) Molecular cloning of the lethal(1)discs large-1 oncogene of Drosophila. Dev. Biol. 134, 222–235.

    PubMed  CAS  Google Scholar 

  99. Makino, K., Kuwahara, H., Masuko, N., et al. (1997) Cloning and characterization of NE-dlg: a novel human homolog of the Drosophila discs large (dlg) tumor suppressor protein interacts with the APC protein. Oncogene 14, 2425–2433.

    PubMed  CAS  Google Scholar 

  100. Hanada, N., Makino, K., Koga, H., et al. (2000) NE-dlg, a mammalian homolog of Drosophila dlg tumor suppressor, induces growth suppression and impairment of cell adhesion: possible involvement of down-regulation of beta-catenin by NE-dlg expression. Int. J. Cancer 86, 480–488.

    PubMed  CAS  Google Scholar 

  101. Bilder, D., Li, M., and Perrimon, N. (2000) Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289, 113–116.

    PubMed  CAS  Google Scholar 

  102. Bilder, D. and Perrimon, N. (2000) Localization of apical epithelial determinants by the basolateral PDZ protein Scribble. Nature 403, 676–680.

    PubMed  CAS  Google Scholar 

  103. Truman, J. W., Taylor, B. J., and Awad, T. A. (1993) Formation of the adult nervous system, in The Development of Drosophila Melanogaster (Bate, M., and Martinez Arias, A., eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N Y, vol. 2, pp. 1245–1276.

    Google Scholar 

  104. Peng, C. Y., Manning, L., Albertson, R., and Doe, C. Q. (2000) The tumour-suppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts. Nature 408, 596–600.

    PubMed  CAS  Google Scholar 

  105. Ohshiro, T., Yagami, T., Zhang, C., and Matsuzaki, F. (2000) Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast. Nature 408, 593–596.

    PubMed  CAS  Google Scholar 

  106. Gateff, E., Loffler, T., and Wismar, J. (1993) A temperature-sensitive brain tumor suppressor mutation of Drosophila melanogaster: developmental studies and molecular localization of the gene. Mech. Dev. 41, 15–31.

    PubMed  CAS  Google Scholar 

  107. Wismar, J., Loffler, T., Habtemichael, N., et al. (1995) The Drosophila melanogaster tumor suppressor gene lethal(3)malignant brain tumor encodes a proline-rich protein with a novel zinc finger. Mech. Dev. 53, 141–154.

    PubMed  CAS  Google Scholar 

  108. Koga, H., Matsui, S., Hirota, T., Takebayashi, S., Okumura, K., and Saya, H. (1999) A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt) protein associates with condensed mitotic chromosomes. Oncogene 18, 3799–3809.

    PubMed  CAS  Google Scholar 

  109. Arama, E., Dickman, D., Kimchie, Z., Shearn, A., and Lev, Z. (2000) Mutations in the betapropeller domain of the Drosophila brain tumor (brat) protein induce neoplasm in the larval brain. Oncogene 19, 3706–3716.

    PubMed  CAS  Google Scholar 

  110. Sonoda, J. and Wharton, R. P. (2001) Drosophila brain tumor is a translational repressor. Genes Dev. 15, 762–773.

    PubMed  CAS  Google Scholar 

  111. Spradling, A. C. (1993) Developmental genetics of oogenesis, in The Development of Drosophila Melanogaster (Bate, M., and Martinez Arias, A., Eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, vol. 1, pp. 1–70

    Google Scholar 

  112. McKearin, D. and Christerson, L. (1994) Molecular genetics of the early stages of germ cell differentiation during Drosophila oogenesis. Ciba Found. Symp. 182, 210–219.

    PubMed  CAS  Google Scholar 

  113. McKearin, D. and Ohlstein, B. (1995) A role for the Drosophila bag-of-marbles protein in the differentiation of cystoblasts from germline stem cells. Development 121, 2937–2947.

    PubMed  CAS  Google Scholar 

  114. Gonczy, P., Matunis, E., and DiNardo, S. (1997) bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis. Development 124, 4361–4371.

    PubMed  CAS  Google Scholar 

  115. Lavoie, C. A., Ohlstein, B., and McKearin, D. M. (1999) Localization and function of Bam protein require the benign gonial cell neoplasm gene product. Dev. Biol. 212, 405–413.

    PubMed  CAS  Google Scholar 

  116. Ohlstein, B., Lavoie, C. A., Vef, O., Gateff, E., and McKearin, D. M. (2000) The Drosophila cystoblast differentiation factor, benign gonial cell neoplasm, is related to DExH-box proteins and interacts genetically with bag-of-marbles. Genetics 155, 1809–1819.

    PubMed  CAS  Google Scholar 

  117. King, R. C. and Storto, P. D. (1988) The role of the otu gene in Drosophila oogenesis. Bioessays 8, 18–24.

    PubMed  CAS  Google Scholar 

  118. Ghelelovitch, S. (1969) Melanotic tumors in Drosophila melanogaster. Natl. Cancer Inst. Monogr. 31, 263–275.

    PubMed  CAS  Google Scholar 

  119. Mathey-Prevot, B. and Perrimon, N. (1998) Mammalian and Drosophila blood: JAK of all trades? Cell 92, 697–700.

    PubMed  CAS  Google Scholar 

  120. Binari, R. and Perrimon, N. (1994) Stripe-specific regulation of pair-rule genes by hopscotch, a putative Jak family tyrosine kinase in Drosophila. Genes Dev. 8, 300–312.

    PubMed  CAS  Google Scholar 

  121. Hanratty, W. P. and Dearolf, C. R. (1993) The Drosophila tumorous-lethal hematopoietic oncogene is a dominant mutation in the hopscotch locus. Mol. Gen. Genet. 238, 33–37.

    PubMed  CAS  Google Scholar 

  122. Harrison, D. A., Binari, R., Nahreini, T. S., Gilman, M., and Perrimon, N. (1995) Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. EMBO J. 14, 2857–2865.

    PubMed  CAS  Google Scholar 

  123. Watson, K. L., Konrad, K. D., Woods, D. F., and Bryant, P. J. (1992) Drosophila homolog of the human S6 ribosomal protein is required for tumor suppression in the hematopoietic system. Proc. Natl. Acad. Sci. USA 89, 11302–11306.

    PubMed  CAS  Google Scholar 

  124. Su, T. T. and O’Farrell, P. H. (1998) Size control: cell proliferation does not equal growth. Curr. Biol. 8, R687–R689.

    PubMed  CAS  Google Scholar 

  125. Johnston, L. A., Prober, D. A., Edgar, B. A., Eisenman, R. N., and Gallant, P. (1999) Drosophila myc regulates cellular growth during development. Cell 98, 779–790.

    PubMed  CAS  Google Scholar 

  126. Ito, N. and Rubin, G. M. (1999) gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. Cell 96, 529–539.

    PubMed  CAS  Google Scholar 

  127. Wolff, T. (2000) Histological techniques for the Drosophila eye. Part II: adult, in Drosophila Protocols (Sullivan, W., Ashburner, M., and Hawley, R. S., eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 229–244.

    Google Scholar 

  128. Sweeney, S. T., Hidalgo, A., deBelle, J. S., and Keshishian, H. (2000) Functional cell ablation, in Drosophila Protocols (Sullivan, W., Ashburner, M., and Hawley, R. S., eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 449–478.

    Google Scholar 

  129. Hay, B. A., Wolff, T., and Rubin, G. M. (1994) Expression of baculovirus P35 prevents cell death in Drosophila. Development 120, 2121–2129.

    PubMed  CAS  Google Scholar 

  130. Brachmann, C. B., Jassim, O. W., Wachsmuth, B. D., and Cagan, R. L. (2000) The Drosophila bcl-2 family member dBorg-1 functions in the apoptotic response to UV-irradiation. Curr. Biol. 10, 547–550.

    PubMed  CAS  Google Scholar 

  131. Han, M. (1992) Ras proteins in developmental pattern formation in Caenorhabditis elegans and Drosophila. Semin. Cancer Biol. 3, 219–228.

    CAS  Google Scholar 

  132. Wassarman, D. A., Therrien, M., and Rubin, G. M. (1995) The Ras signaling pathway in Drosophila. Curr. Opin. Genet. Dev. 5, 44–50.

    PubMed  CAS  Google Scholar 

  133. Miller, J. R. and Moon, R. T. (1996) Signal transduction through beta-catenin and specification of cell fate during embryogenesis. Genes Dev. 10, 2527–2539.

    PubMed  CAS  Google Scholar 

  134. Currie, P. D. (1998) Hedgehog’s escape from Pandora’s box. J. Mol. Med. 76, 421–433.

    PubMed  CAS  Google Scholar 

  135. Stern, D. L. and Sucena, E. (2000) Preparation of larval and adult cuticles for light microscopy, in Drosophila Protocols (Sullivan, W., Ashburner, M., and Hawley, R. S., eds.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 601–616.

    Google Scholar 

  136. Casci, T. and Freeman, M. (1999) Control of EGF receptor signalling: lessons from fruitflies. Cancer Metastasis Rev. 18, 181–201.

    PubMed  CAS  Google Scholar 

  137. Nilson, L. A. and Schupbach, T. (1999) EGF receptor signaling in Drosophila oogenesis. Curr. Top. Dev. Biol. 44, 203–243.

    PubMed  CAS  Google Scholar 

  138. Wasserman, J. D. and Freeman, M. (1998) An autoregulatory cascade of EGF receptor signaling patterns the Drosophila egg. Cell 95, 355–364.

    PubMed  CAS  Google Scholar 

  139. Basler, K. and Struhl, G. (1994) Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein. Nature 368, 208–214.

    PubMed  CAS  Google Scholar 

  140. Robinow, S. and White, K. (1988) The locus elav of Drosophila melanogaster is expressed in neurons at all developmental stages. Dev. Biol. 126, 294–303.

    PubMed  CAS  Google Scholar 

  141. Hynes, R. O. and Zhao, Q. (2000) The evolution of cell adhesion. J. Cell Biol. 150, F89–F96.

    PubMed  CAS  Google Scholar 

  142. Tepass, U. (1999) Genetic analysis of cadherin function in animal morphogenesis. Curr. Opin. Cell Biol. 11, 540–548.

    PubMed  CAS  Google Scholar 

  143. Takeichi, M., Nakagawa, S., Aono, S., Usui, T., and Uemura, T. (2000) Patterning of cell assemblies regulated by adhesion receptors of the cadherin superfamily. Phil. Trans. R. Soc. Lond. B, Biol. Sci. 355, 885–890.

    CAS  Google Scholar 

  144. Brown, N. H. (2000) Cell-cell adhesion via the ECM: integrin genetics in fly and worm. Matrix Biol. 19, 191–201.

    PubMed  CAS  Google Scholar 

  145. Brown, N. H., Gregory, S. L., and Martin-Bermudo, M. D. (2000) Integrins as mediators of morphogenesis in Drosophila. Dev. Biol. 223, 1–16.

    PubMed  CAS  Google Scholar 

  146. Brower, D. L., Brabant, M. C., and Bunch, T. A. (1995) Role of the PS integrins in Drosophila development. Immunol. Cell Biol. 73, 558–564.

    PubMed  CAS  Google Scholar 

  147. Murray, M. A., Fessler, L. I., and Palka, J. (1995) Changing distributions of extracellular matrix components during early wing morphogenesis in Drosophila. Dev. Biol. 168, 150–165.

    PubMed  CAS  Google Scholar 

  148. Walsh, E. P. and Brown, N. H. (1998) A screen to identify Drosophila genes required for integrin-mediated adhesion. Genetics 150, 791–805.

    PubMed  CAS  Google Scholar 

  149. Forbes, A. and Lehmann, R. (1999) Cell migration in Drosophila. Curr. Opin. Genet. Dev. 9, 473–478.

    PubMed  CAS  Google Scholar 

  150. Montell, D. J. (1999) The genetics of cell migration in Drosophila melanogaster and Caenorhabditis elegans development. Development 126, 3035–3046.

    PubMed  CAS  Google Scholar 

  151. Gomperts, M., Wylie, C., and Heasman, J. (1994) Primordial germ cell migration. Ciba Found. Symp. 182, 121–134.

    PubMed  CAS  Google Scholar 

  152. Jaglarz, M. K. and Howard, K. R. (1995) The active migration of Drosophila primordial germ cells. Development 121, 3495–3503.

    PubMed  CAS  Google Scholar 

  153. Saffman, E. E. and Lasko, P. (1999) Germline development in vertebrates and invertebrates. Cell Mol. Life Sci. 55, 1141–1163.

    PubMed  CAS  Google Scholar 

  154. Bai, J., Uehara, Y., and Montell, D. J. (2000) Regulation of invasive cell behavior by taiman, a Drosophila protein related to AIB1, a steroid receptor coactivator amplified in breast cancer. Cell 103, 1047–1058.

    PubMed  CAS  Google Scholar 

  155. Chen, J., Godt, D., Gunsalus, K., Kiss, I., Goldberg, M., and Laski, F. A. (2001) Cofilin/ADF is required for cell motility during Drosophila ovary development and oogenesis. Nat. Cell Biol. 3, 204–209.

    PubMed  CAS  Google Scholar 

  156. Fox, G. L., Rebay, I., and Hynes, R. O. (1999) Expression of DFak56, a Drosophila homolog of vertebrate focal adhesion kinase, supports a role in cell migration in vivo. Proc. Natl. Acad. Sci. USA 96, 14978–14983.

    PubMed  CAS  Google Scholar 

  157. Lee, T., Feig, L., and Montell, D. J. (1996) Two distinct roles for Ras in a developmentally regulated cell migration. Development 122, 409–418.

    PubMed  CAS  Google Scholar 

  158. Lee, T. and Montell, D. J. (1997) Multiple Ras signals pattern the Drosophila ovarian follicle cells. Dev. Biol. 185, 25–33.

    PubMed  CAS  Google Scholar 

  159. Murphy, A. M. and Montell, D. J. (1996) Cell type-specific roles for Cdc42, Rac, and RhoL in Drosophila oogenesis. J. Cell Biol. 133, 617–630.

    PubMed  CAS  Google Scholar 

  160. Niewiadomska, P., Godt, D., and Tepass, U. (1999) DE-Cadherin is required for intercellular motility during Drosophila oogenesis. J. Cell Biol. 144, 533–547.

    PubMed  CAS  Google Scholar 

  161. Hing, H., Xiao, J., Harden, N., Lim, L., and Zipursky, S. L. (1999) Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila. Cell 97, 853–863.

    PubMed  CAS  Google Scholar 

  162. Henderson, D. S. (1999) DNA repair defects and other (mus)takes in Drosophila melanogaster. Methods 18, 377–400.

    PubMed  CAS  Google Scholar 

  163. Morris, J. and Lehmann, R. (1999) Drosophila oogenesis: versatile spn doctors. Curr. Biol. 9, R55–R58.

    PubMed  CAS  Google Scholar 

  164. Vogel, E. W. and Nivard, M. J. (1993) Performance of 181 chemicals in a Drosophila assay predominantly monitoring interchromosomal mitotic recombination. Mutagenesis 8, 57–81.

    PubMed  CAS  Google Scholar 

  165. Ghabrial, A., Ray, R. P., and Schupbach, T. (1998) okra and spindle-B encode components of the RAD52 DNA repair pathway and affect meiosis and patterning in Drosophila oogenesis. Genes Dev. 12, 2711–2723.

    PubMed  CAS  Google Scholar 

  166. Karim, F. D., Chang, H. C., Therrien, M., Wassarman, D. A., Laverty, T., and Rubin, G. M. (1996) A screen for genes that function downstream of Ras1 during Drosophila eye development. Genetics 143, 315–329.

    PubMed  CAS  Google Scholar 

  167. Avery, L. and Wasserman, S. (1992) Ordering gene function: the interpretation of epistasis in regulatory hierarchies. Trends Genet. 8, 312–316.

    PubMed  CAS  Google Scholar 

  168. Guarente, L. (1993) Synthetic enhancement in gene interaction: a genetic tool come of age. Trends Genet. 9, 362–366.

    PubMed  CAS  Google Scholar 

  169. Giordano, A. and Kaiser, H. E. (1996) The retinoblastoma gene: its role in cell cycle and cancer. In Vivo 10, 223–227.

    PubMed  CAS  Google Scholar 

  170. Metzger, R. J. and Krasnow, M. A. (1999) Genetic control of branching morphogenesis. Science 284, 1635–1639.

    PubMed  CAS  Google Scholar 

  171. Zelzer, E. and Shilo, B. Z. (2000) Cell fate choices in Drosophila tracheal morphogenesis. Bioessays 22, 219–226.

    PubMed  CAS  Google Scholar 

  172. Jarecki, J., Johnson, E., and Krasnow, M. A. (1999) Oxygen regulation of airway branching in Drosophila is mediated by branchless FGF. Cell 99, 211–220.

    PubMed  CAS  Google Scholar 

  173. Echalier, G. (1997) Drosophila continuous cell lines, in Drosophila Cells in Culture (Echalier, G., ed.). Morgan Kaufmann, San Francisco, CA, pp. 131–187.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT

    Raymond A. Pagliarini & Tian Xu

  2. Yale University School of Medicine, New Haven, CT

    Ana T. Quiñones

Authors
  1. Raymond A. Pagliarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana T. Quiñones
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tian Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA

    Wafik S. El-Deiry MD, PhD

  2. Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA

    Wafik S. El-Deiry MD, PhD

  3. Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA

    Wafik S. El-Deiry MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Humana Press Inc.

About this protocol

Cite this protocol

Pagliarini, R.A., Quiñones, A.T., Xu, T. (2003). Analyzing the Function of Tumor Suppressor Genes Using a Drosophila Model. In: El-Deiry, W.S. (eds) Tumor Suppressor Genes. Methods in Molecular Biology™, vol 223. Humana Press. https://doi.org/10.1385/1-59259-329-1:349

Download citation

  • DOI: https://doi.org/10.1385/1-59259-329-1:349

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-987-2

  • Online ISBN: 978-1-59259-329-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation