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Expression of genes related to apoptosis, cell cycle and signaling pathways are independent of TP53 status in urinary bladder cancer cells

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Abstract

Urinary bladder cancer is the fourth most common malignancy in the Western world. Transitional cell carcinoma (TCC) is the most common subtype, accounting for about 90% of all bladder cancers. The TP53 gene plays an essential role in the regulation of the cell cycle and apoptosis and therefore contributes to cellular transformation and malignancy; however, little is known about the differential gene expression patterns in human tumors that present with the wild-type or mutated TP53 gene. Therefore, because gene profiling can provide new insights into the molecular biology of bladder cancer, the present study aimed to compare the molecular profiles of bladder cancer cell lines with different TP53 alleles, including the wild type (RT4) and two mutants (5637, with mutations in codons 280 and 72; and T24, a TP53 allele encoding an in-frame deletion of tyrosine 126). Unsupervised hierarchical clustering and gene networks were constructed based on data generated by cDNA microarrays using mRNA from the three cell lines. Differentially expressed genes related to the cell cycle, cell division, cell death, and cell proliferation were observed in the three cell lines. However, the cDNA microarray data did not cluster cell lines based on their TP53 allele. The gene profiles of the RT4 cells were more similar to those of T24 than to those of the 5637 cells. While the deregulation of both the cell cycle and the apoptotic pathways was particularly related to TCC, these alterations were not associated with the TP53 status.

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References

  1. Kirkali Z, Chan T, Manoharan M, Algaba F, Busch C, Cheng L, Kiemeney L, Kriegmair M, Montironi R, Murphy WM, Sesterhenn IA, Tachibana M, Weider J (2005) Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology 66:4–34

    Article  PubMed  Google Scholar 

  2. Cookson MS, Herr W, Zhang ZF, Soloway S, Sogani PC, Fair WR (1997) The treated natural history of high risk superficial bladder cancer: 15-year outcome. J Urol 158:62–67

    Article  PubMed  CAS  Google Scholar 

  3. Nishiyama H, Habuchi T, Watanabe J, Teramukai S, Tada H, Ono Y, Ohshima S, Fujimoto K, Hirao Y, Fukushima M, Ogawa O (2004) Clinical outcome of a large-scale multi-institutional retrospective study for locally advanced bladder cancer: a survey including 1131 patients treated during 1990–2000 in Japan. Eur Urol 45:176–181

    Article  PubMed  Google Scholar 

  4. Cordon-Cardo C (2008) Molecular alterations associated with bladder cancer initiation and progression. Scand J Urol Nephrol Suppl 218:154–165

    Article  PubMed  Google Scholar 

  5. Wolff EM, Liang G, Jones PA (2005) Mechanisms of disease: genetic and epigenetic alterations that drive bladder cancer. Nat Clin Pract Urol 2:502–510

    Article  PubMed  CAS  Google Scholar 

  6. Levine A (2005) The p53 tumor-suppressor gene. N Engl J Med 1992(326):1350–1352

    Google Scholar 

  7. Sengupta S, Harris CC (2005) p53: traffic cop at the crossroads of DNA repair and recombination. Nat Rev Mol Cell Biol 6:44–55

    Article  PubMed  CAS  Google Scholar 

  8. Sanchez-Carbayo M, Socci ND, Charytonowicz E, Lu M, Prystowsky M, Childs G, Cordon-Cardo C (2002) Molecular profiling of bladder cancer using cDNA microarrays: defining histogenesis and biological phenotypes. Cancer Res 62:6973–6980

    PubMed  CAS  Google Scholar 

  9. Sanchez-Carbayo M, Socci ND, Richstone L, Corton M, Behrendt N, Wulkfuhle J, Bochner B, Petricoin E, Cordon-Cardo C (2007) Genomic and proteomic profiles reveal the association of gelsolin to TP53 status and bladder cancer progression. Am J Pathol 171:1650–1658

    Article  PubMed  CAS  Google Scholar 

  10. Coppée J-Y (2008) Do DNA microarrays have their future behind them? Microbes Infect 10:1067–1071

    Article  PubMed  Google Scholar 

  11. Grant GR, Manduchi E, Stoeckert Jr CJ (2007) Analysis and management of microarray gene expression data. Curr Protoc Mol Biol, Chapter 19: Unit 19.6

  12. Kraemer K, Schmidt U, Fuessel S, Herr A, Wirth MP, Meye A (2006) Microarray analyses in bladder cancer cells: inhibition of hTERT expression down-regulates EGFR. Int J Cancer 119:1276–1284

    Article  PubMed  CAS  Google Scholar 

  13. Kikuchi T, Daigo Y, Katagiri T, Tsunoda T, Okada K, Kakiuchi S, Zembutsu H, Furukawa Y, Kawamura M, Kobayashi K, Imai K, Nakamura Y (2003) Expression profiles of non-small cell lung cancers on cDNA microarrays: Identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene 22:2192–2205

    Article  PubMed  CAS  Google Scholar 

  14. Staege M, Banning-Eichenseer U, Weibflog G, Volkmer I, Burdach S, Richter G, Mauz-Korholz C, Foll J, Korholz D (2008) Gene expression profiles of Hodgkin’s lymphoma cell lines with different sensitivity to cytotoxic drugs. Exp Hematol 36:886–896

    Article  PubMed  CAS  Google Scholar 

  15. Cooper MJ, Haluschak JJ, Johsond D, Schwartz S, Morrison LJ, Lippa M, Hatzivassiliou G, Tan J (1994) p53 mutations in bladder carcinoma cell lines. Oncol Res 6:569–579

    PubMed  CAS  Google Scholar 

  16. Rieger KM, Little AF, Swart JM, Kastrinakis WV, Fitzgerald JM, Hess DT, Libertino JA, Summerhayes IC (1995) Human bladder carcinoma cell lines as indicators of oncogenic change relevant to urothelial neoplastic progression. Br J Cancer 72:683–690

    Article  PubMed  CAS  Google Scholar 

  17. da Silva GN, Marcondes JPC, Camargo EA, Passos GAS, Sakamoto-Hojo ET, Salvadori DMF (2010) Cell cycle arrest and apoptosis in TP53 subtypes of bladder carcinoma cell lines treated with cisplatin and gemcitabine. Exp Biol Med 235:814–824

    Article  CAS  Google Scholar 

  18. Hegde P, Qi R, Abernathy K, Gay C, Dharap S, Gaspard R, Hughes JE, Snesrud E, Lee N, Quackenbush J (2000) A concise guide to cDNA microarray analysis. Biotechniques 29: 548–550, 552–544, 556 passim

    Google Scholar 

  19. Spot software [http://www.tm4.org/spotfinder.html]

  20. Ihaka R, Gentleman R (1996) A language for data analysis and graphics. J Comput Graph Stat 5:299–314

    Article  Google Scholar 

  21. KTH package [http://www.biotech.kth.se/molbio/microarray/]

  22. Yang YH, Speed T (2002) Design issues for cDNA microarray experiments. Nat Rev Genet 3:579–588

    PubMed  CAS  Google Scholar 

  23. MEV software [http://www.tm4.org/mev.html]

  24. S.O.U.R.C.E. [http://smd-www.stanford.edu/cgi-bin/source/sourceSearch]

  25. NCBI [http://www.ncbi.nlm.nih.gov/]

  26. FATIGO [http://babelomics.bioinfo.cipf.es/]

  27. Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. PNAS 98:5116–5121

    Article  PubMed  CAS  Google Scholar 

  28. Gene Network [http://idv.sinica.edu.tw/hchuang/GeneNetwork1.2Setup.exe]

  29. Blaveri E, Simko JP, James JE, Brewer JL, Baehner F, DeVries KS, Koppie T, Pejavar S, Carroll P, Waldman F (2005) Bladder cancer outcome and subtype classification by gene expression. Clin Cancer Research 11:4044–4055

    Article  CAS  Google Scholar 

  30. Kato S (2003) Understanding the function structure and function mutation relationships of p53 tumor suppressor protein by high resolution missense mutation analysis. Proc Natl Acad Sci USA 100:8424–8429

    Article  PubMed  CAS  Google Scholar 

  31. Brosh R, Rotter V (2009) When mutations gain new powers: news from the mutant p53 field. Nat Rev Cancer 10:701–713

    Article  Google Scholar 

  32. Prives C, Manfredi JJ (2005) The continuing saga of p53—More sleepless nighs ahead. Mol Cell 19:719–721

    Article  PubMed  CAS  Google Scholar 

  33. Zhao S, Zhang J, Zhang X, Dong X, Sun X (2008) Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep 35:421–429

    Article  PubMed  CAS  Google Scholar 

  34. Savopoulos JW, Carter PS, Turconi S, Pettman GR, Karran EH, Gray CW, Ward RV, Jenkins O, Creasy CL (2000) Expression, purification, and functional analysis of the human serine protease HtrA2. Protein Expr Purif 19:227–234

    Article  PubMed  CAS  Google Scholar 

  35. Muzio M, Stockwell BR, Stennicke HR, Salvesen GS, Dixit VM (1998) An induced proximity model for caspase-8 activation. J Biol Chem 273:2926–2930

    Article  PubMed  CAS  Google Scholar 

  36. Ding SJ, Li Y, Shao XX, Zhou H, Zeng R, Tang ZY, Xiav QC (2004) Proteome analysis of hepatocellular carcinoma cell strains, MHCC97-H and MHCC97-L, with different metastasis potentials. Proteomics 4:982–994

    Article  PubMed  CAS  Google Scholar 

  37. Hinata N, Shirakawa T, Zhang Z, Matsumoto A, Fujisawa M, Okada H, Kamidono S, Gotoh A (2003) Radiation induces p53-dependent cell apoptosis in bladder câncer cells with wild-type-p53 but not in p53-mutated bladder cancer cells. Urol Res 31:387–396

    Article  PubMed  CAS  Google Scholar 

  38. Esrig D, Spruck CH 3rd, Nichols PW, Chaiwun B, Steven K, Groshen S, Chen SC, Skinner DG, Jones PA, Cote RJ (1993) p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer. Am J Pathol 143:1389–1397

    PubMed  CAS  Google Scholar 

  39. Fujita T, Kobayashi Y, Wada O, Tateishi Y, Kitada L, Yamamoto Y, Takashima H, Murayama A, Yano T, Baba T, Kato S, Kawabe Y-I, Yanagisawa J (2003) Full activation of estrogen receptor—activation function-1 induces proliferation of breast cancer cells. J Biol Chemistry 29:26704–26714

    Article  Google Scholar 

  40. Hecker C-M, Rabiller M, Haglund K, Bayer P, Dikic I (2006) Specification of SUMO1- and SUMO2-interacting motifs. J Biol Chemistry 281:16117–16127

    Article  CAS  Google Scholar 

  41. Niki T, Galli I, Ariga H, Iguchi-Ariga SMM (2000) MSSP, a protein binding to an origin of replication in the c-myc gene, interacts with a catalytic subunit of DNA polymerase α and stimulates its polymerase activity. FEBS Letters 475:209–212

    Article  PubMed  CAS  Google Scholar 

  42. Kortmansky J, Shah MA, Kaubisch A (2005) Phase I trial of thecyclin-dependent kinase inhibitor and protein kinase C inhibitor 7-hydroxystaurosporine in combination with fluorouracil in patients with advanced solid tumors. J Clin Oncol 23:1875–1884

    Article  PubMed  CAS  Google Scholar 

  43. Hart FU (1996) Molecular chaperones in cellular protein folding. Nature 381:571–579

    Article  Google Scholar 

  44. Moussa O, Yordy JS, Abol-Enein H, Sinha D, Bissada NK, Haluska PV, Ghoneim MA, Watson DK (2005) Prognostic and functional significance of thromboxane synthase gene overexpression in invasive bladder cancer. Cancer Res 65:11581–11587

    Article  PubMed  CAS  Google Scholar 

  45. Macheda ML, Rogers S, Best JD (2005) Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 2202:654–662

    Article  Google Scholar 

  46. Yang Q, Liu S, Tian Y, Hasan C, Kersey D, Salwen HR, Chlenski A, Perlman EJ, Cohn SL (2004) Methylation-associated silencing of the heat shock protein 47 gene in human neuroblastoma. Cancer Res 64:4531–4538

    Article  PubMed  CAS  Google Scholar 

  47. Wang L, He G, Zhang P, Wang X, Jiang M, Yu L (2010) Interplay between MDM2, MDMX, Pirh2 and COP1: the negative regulators of p53. Mol Biol Rep [Epub ahead of print]

  48. Yuan J, Tang W, Luo K, Chen X, Gu X, Wan B, Yu L (2006) Cloning and characterization of the human gene DERP6, which activates transcriptional activities of p53. Mol Biol Rep 33:151–158

    Article  PubMed  CAS  Google Scholar 

  49. Soussi T, Wiman KG (2007) Shaping genetic alterations in human cancer: the p53 mutation paradigm. Cancer Cell 12:303–312

    Article  PubMed  CAS  Google Scholar 

  50. Guerreiro Da Silva IS, Hu YF, Russo IH, Ao X, Salicioni AM, Yang X, Russo J (2000) S100P calciumbinding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo. Int J Oncol 16:231–240

    PubMed  CAS  Google Scholar 

  51. Oegema K, Savoian MS, Matchinson TJ, Field CM (2000) Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis. J Cell Biol 150:539–551

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), Brazil.

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None.

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Authors and Affiliations

  1. Faculdade de Medicina de Botucatu, Botucatu Medical School, UNESP—São Paulo State University, Botucatu, SP, 18618-000, Brazil

    Glenda N. da Silva & Daisy M. F. Salvadori

  2. USP—University of São Paulo, Faculty of Medicine, Ribeirão Preto, SP, Brazil

    Adriane F. Evangelista, Danielle A. Magalhães, Cláudia Macedo, Elza T. Sakamoto-Hojo & Geraldo A.S. Passos

  3. UNESP—São Paulo State University, Biosciences Institute, Botucatu, SP, Brazil

    Michelle C. Búfalo

  4. USP—University of São Paulo Department of Biology (FFCLRP), Ribeirão Preto, SP, Brazil

    Elza T. Sakamoto-Hojo

  5. USP—University of São Paulo Faculty of Dentistry, Ribeirão Preto, SP, Brazil

    Geraldo A.S. Passos

Authors
  1. Glenda N. da Silva
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  2. Adriane F. Evangelista
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  3. Danielle A. Magalhães
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  4. Cláudia Macedo
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  5. Michelle C. Búfalo
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  6. Elza T. Sakamoto-Hojo
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  7. Geraldo A.S. Passos
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  8. Daisy M. F. Salvadori
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Corresponding author

Correspondence to Glenda N. da Silva.

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Authors contributions

“All authors reviewed the manuscript. GNS was responsible for the study design and interpretation of the data; performed most of the experiments and wrote the manuscript. AFE was responsible for constructing the gene networks. DAM and CM conducted the cDNA microarray experiments. MCB conducted the real-time qPCR experiments. GASP and ETSH contributed to the interpretation of data and provided critical readings of the manuscript. DMFS contributed to the study design and interpretation of the data, as well as provided a critical reading of the manuscript.”

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da Silva, G.N., Evangelista, A.F., Magalhães, D.A. et al. Expression of genes related to apoptosis, cell cycle and signaling pathways are independent of TP53 status in urinary bladder cancer cells. Mol Biol Rep 38, 4159–4170 (2011). https://doi.org/10.1007/s11033-010-0536-x

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  • DOI: https://doi.org/10.1007/s11033-010-0536-x

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