Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27

Abstract

Cytogenetic, molecular and functional analysis has shown that chromosome region 6q27 harbors a senescence inducing gene and a tumor suppressor gene involved in several solid and hematologic malignancies. We have cloned at 6q27 and characterized the RNASE6PL gene which belongs to a family of cytoplasmic RNases highly conserved from plants, to man. Analysis of 55 primary ovarian tumors and several ovarian tumor cell lines indicated that the RNASE6PL gene is not mutated in tumor tissues, but its expression is significantly reduced in 30% of primary ovarian tumors and in 75% of ovarian tumor cell lines. The promoter region of the gene was unaffected in tumors cell lines. Transfection of RNASE6PL cDNA into HEY4 and SG10G ovarian tumor cell lines suppressed tumorigenicity in nude mice. When tumors were induced by RNASE6PL-transfected cells, they completely lacked expression of RNASE6PL cDNA. Tumorigenicity was suppressed also in RNASE6PL-transfected pRPcT1/H6cl2T cells, derived from a human/mouse monochromosomic hybrid carrying a human chromosome 6 deleted at 6q27. Moreover, 63.6% of HEY4 clones and 42.8% of the clones of XP12ROSV, a Xeroderma pigmentosum SV40-immortalized cell line, transfected with RNASE6PL cDNA, developed a marked senescence process during in vitro growth. We therefore propose that RNASE6PL may be a candidate for the 6q27 senescence inducing and class II tumor suppressor gene in ovarian cancer.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Abdollahi A, Godwin A, Miller P, Getts L, Schultz D, Taguchi T, Testa J and Hamilton T. . 1997 Cancer Res. 57: 2029–2034.

  • Acquati F, Nucci C, Bianchi M and Taramelli R. . 2000 Meth. Mol. Biol. (in press).

  • Anderson M, Cornish E, Mau S, Williams E, Hoggart R, Atkinson A, Bonig I, Grego B, Simpson R, Roche P, Penschow J and Clarke A. . 1986 Nature 321: 38–41.

  • Ardelt W, Mikulsky S and Shogen K. . 1991 J. Biol. Chem. 266: 245–251.

  • Banga S, Kim S, Hubbard K, Dasgupta T, Jha K, Patsalis P, Hauptschein R, Gamberi B, Dalla Favera R, Kraemer P and Ozer H. . 1997 Oncogene 14: 313–321.

  • Baylin S and Herman J. . 2000 Trends Genet. 16: 168–174.

  • Bilanges B, Varrault A, Basyuk E, Rodriguez C, Mazumdar A, Pantaloni C, Bockaert J, Theillet C, Spengler D and Journot L. . 1999 Oncogene 18: 3979–3983.

  • Bruening W, Prowse A, Schultz D, Holgado Madruga M, Wong A and Gowin A. . 1999 Cancer Res. 59: 4973–4983.

  • Buick RN, Pullano R and Trent JM. . 1985 Cancer Res. 45: 3668–3676.

  • Chappell S, Walsh T, Walker R and Show J. . 1997 Br. J. Cancer 75: 1324–1329.

  • Clark K, Okuley J, Collins P and Sims T. . 1990 Plant Cell 2: 815–826.

  • Colitti C, Rodabaugh K, Welch W, Berkowitz R and Mok S. . 1998 Oncogene 16: 555–559.

  • Cooke I, Cox S, Shelling A, LeMeuth V, Charnock M and Ganesan T. . 1996 Genes Chromosomes Cancer 15: 13–20.

  • D'Alessio G. . 1993 Trends Cell. Biol. 3: 106–109.

  • De Souza A, Hankins G, Washington M, Fine R, Orton T and Jirtle R. . 1995 Oncogene 10: 1725–1729.

  • Develee P, van Vliet M, van Sloun Kuipers N, Hermans J, Pearson P and Cornelisse C. . 1991 Oncogene 6: 1705–1711.

  • Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I and Pereira-Smith O. . 1995 Proc. Natl. Acad. Sci. USA 92: 9363–9367.

  • Foulkes W, Ragoussis J, Stamp G, Allan G and Trowsdale J. . 1993 Br. J. Cancer 67: 551–559.

  • Francesconi M, Meryn S, Rogan AM, Szalay S, Graninger W and Schmidbauer CP. . 1984 Cancer 53: 1927–1930.

  • Gaidano G, Hauptschein R, Parsa N, Offit K, Rao P, Lenoir G, Knowles D, Chaganti R and Dalla Favera R. . 1992 Blood 80: 1781–1787.

  • Garzetti GG, Possati L, Ciavattini A, Recanatini E, Cignitti M, Valensise H and Romanini C. . 1992 Eur. J. Gynaecol. Oncol. 13: 514–521.

  • Gualandi F, Morelli C, Pavan JV, Rimessi P, Sensi A, Bonfatti A, Gruppioni R, Possati L, Stanbridge EJ and Barbanti-Brodano G. . 1994 Genes Chrom. Cancer 10: 77–84.

  • Haber D and Harlow E. . 1997 Nature Genet. 16: 320–322.

  • Hauptschein R, Gamberi B, Pulivarthi R, Frigri F, Scotto L, Venkatraj, Gaidano G, Rutner T, Edwards Y, Chaganti R and Dalla-Favera R. . 1998 Genomics 50: 170–186.

  • Hayashi Y, Raimondi S, Look T, Behm F, Kitchington G, Pui C, Rivera G and Williams D. . 1990 Blood 76: 1626–1630.

  • Herman J, Graff J, Myohannen S, Nelkin B and Baylin S. . 1996 Proc. Natl. Acad. Sci. USA 93: 9821–9826.

  • Hime G, Prior L and Saint R. . 1995 Gene 158: 203–207.

  • Honchel R, McDonnell S, Schaid D and Thibodeau S. . 1996 Cancer Res. 56: 145–149.

  • Jones P and Laird P. . 1999 Nature Genet. 21: 163–167.

  • Lin H, Huber R, Schlessinger D and Morin P. . 1999 Cancer Res. 59: 807–810.

  • McClure B, Haring V, Ebert P, Anderson M, Simpson R, Sakiyama F and Clarke A. . 1989 Nature 342: 955–957.

  • McClure B, Gray J, Anderson M and Clarke A. . 1990 Nature 347: 757–760.

  • Meador J and Kennell D. . 1990 Gene 95: 1–7.

  • Millikin D, Meese E, Vogelstein B, Witkowski C and Trent J. . 1991 Cancer Res. 51: 5449–5453.

  • Mok S, Chan W, Wong K, Muto M and Berkowitz R. . 1996 Oncogene 12: 1895–1901.

  • Mok S, Chan W, Wong K, Cheung K, Lau C, Ng S, Baldini A, Colitti C, Rock C and Berkowitz R. . 1998 Oncogene 16: 2381–2387.

  • Morita R, Saito S, Ishikawa J, Ogawa O, Yoshida O, Yamakawa K and Nakamura Y. . 1991 Cancer Res. 51: 5817–5820.

  • Orphanos V, McGown G, Hey Y, Thorncroft M, Santibanez-Koref M, Russell S, Hickey I, Atkinson R and Boyle J. . 1995 Br. J. Cancer 71: 666–669.

  • Queimado L, Seruca R, Costa-Pereira and Castedo S. . 1995 Genes Chromosomes Cancer 14: 28–34.

  • Queimado L, Reis A, Fonseca I, Marins C, Lovett M, Soares J and Parreira L. . 1998 Oncogene 16: 83–88.

  • Saito S, Saito H, Sagae S, Kudo R, Saito J, Noda K and Nakamura Y. . 1992 Cancer Res. 52: 5815–5817.

  • Saito S, Sirahama S, Matsushima M, Suzuki M, Sagae S, Kudo R, Saito J, Noda K and Nakamura Y. . 1996 Cancer Res. 56: 5586–5589.

  • Schein C. . 1997 Nature Biotech. 15: 529–536.

  • Schneider R, Unger G, Stark R, Scheider-Scherzer E and Thiel H. . 1993 Science 261: 1169–1171.

  • Shridhar V, Staub J, Huntley B, Cliby W, Jenkins R, Pass H, Hartmann L and Smith D. . 1999 Oncogene 18: 3913–3918.

  • Simon L, Hazard RM, Maher VM and McCormick JJ. . 1981 Carcinogenesis 2: 567–570.

  • Smith MR, Newton DL, Mikulski SM and Rybak SM. . 1999 Exp. Cell. Res. 247: 220–232.

  • Tahara H, Smith A, Gas R, Cryns V and Arnold A. . 1996 Cancer Res. 56: 599–605.

  • Theile M, Seitz S, Arnold W, Jandrig B, Frege R, Schlag P, Haensch W, Barret J and Scherneck S. . 1996 Oncogene 13: 677–685.

  • Tibiletti MG, Bernasconi B, Furlan D, Riva C, Trubia M, Buraggi G, Franchi M, Bolis P, Mariani A, Frigerio L, Capella C and Taramelli R. . 1996 Cancer Res. 56: 4493–4498.

  • Tibiletti M, Bernasconi B, Taborelli M, Furlan D, Fabbri A, Taramelli R, Trubia M and Capella C. . 1997 Br. J. Cancer 75: 1831–1835.

  • Tibiletti MG, Trubia M, Ponti E, Sessa L, Acquati F, Furlan D, Bernasconi B, Fichera M, Mihalich A, Ziegler A, Volz A, Facco C, Riva C, Cremonesi L, Ferrari M and Taramelli R. . 1998 Oncogene 16: 1639–1642.

  • Tibiletti MG, Sessa F, Bernasconi B, Cerutti R, Broggi B, Furlan D, Acquati F, Russo A, Capella C and Taramelli R. . 2000 Clin. Cancer Res. 6: 1422–1431.

  • Trubia M, Sessa L and Taramelli R. . 1997 Genomics 42: 342–344.

  • Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, Cuevas B, Kou W, Gray J, Siciliano M, Mills G and Bast R. . 1999 Proc. Natl. Acad. Sci. USA 96: 214–219.

Download references

Acknowledgements

R Taramelli was supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC) and MURST Cofin 1998. L Possati and G Barbanti-Brodano were supported by grants from AIRC and MURST ex 60% and Cofin 1998.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Acquati, F., Morelli, C., Cinquetti, R. et al. Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27. Oncogene 20, 980–988 (2001). https://doi.org/10.1038/sj.onc.1204178

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204178

Keywords

This article is cited by

Search

Quick links