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Characterization of the gene encoding pinin/DRS/memA and evidence for its potential tumor suppressor function

Oncogene volume 19, pages 289–297 (2000)Cite this article

Abstract

Several cell adhesion-related proteins have been shown to act as tumor-suppressors (TS) in the neoplastic progression of epithelial-derived tumors. Pinin/DRS/memA was first identified in our laboratory and it was shown to be a cell adhesion-related molecule. Our previous study demonstrated that restoration of pinin expression in transformed cells not only positively influenced cellular adhesive properties but also reversed the transformed phenotype to more epithelial-like. Here, we show by FISH analysis that the gene locus for pinin is within 14q13. The alignment of the pinin gene with STS markers localized the gene to the previously identified TS locus D14S75-D14S288. Northern analyses revealed diminished pinin mRNA in renal cell carcinomas (RCC) and certain cancer cell lines. Immunohistochemical examination of tumor samples demonstrated absent or greatly reduced pinin in transitional cell carcinoma (TCC) and RCC tumors. TCC-derived J82 cells as well as EcR-293 cells transfected with full-length pinin cDNA demonstrated inhibition of anchorage-independent growth of cells in soft agar. Furthermore, methylation analyses revealed that aberrant methylation of pinin CpG islands was correlated with decreased/absent pinin expression in a subset of tumor tissues. These data lend significant support to the hypothesis that pinin/DRS/memA may act as a tumor suppressor in certain types of cancers.

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References

  • Bandera CA, Takahashi H, Behbakht K, Liu PC, LiVolsi VA, Benjamin I, Morgan MA, King SA, Rubin SC and Boyd J . 1997 Cancer Res 57: 513–515.

  • Baylin SB, Herman JG, Graff JR, Vertino PM and Issa JP . 1998 Adv Cancer Res 72: 141–196.

  • Ben-Ze'ev A . 1997 Curr Opin Cell Biol 9: 99–108.

  • Ben-Ze'ev A and Geiger B . 1998 Curr Opin Cell Biol 10: 629–639.

  • Benedict WF, Lerner SP, Zhou J, Shen X, Tokunaga H and Czerniak B . 1999 Oncogene 18: 1197–1203.

  • Beroud C, Fournet JC, Jeanpierre C, Droz D, Bouvier R, Froger D, Chretien Y, Marechal JM, Weissenbach J and Junien C . 1996 Genes Chromosomes Cancer 17: 215–224.

  • Berx G, Becker KF, Hofler H and Van Roy F . 1998 Hum Mutat 12: 226–237.

  • Birchmeier W . 1995 Bioessays 17: 97–99.

  • Birchmeier W, Behrens J, Weidner KM, Hulskem J and Birchmeier C . 1996 Curr Top Microbiol Immunol 213: 117–135.

  • Brandner JM, Reidenbach S and Franke WW . 1997 Differentiation 62: 119–127.

  • Bullions LC, Notterman DA, Chung LS and Levine AJ . 1997 Mol Cell Biol 17: 4501–4508.

  • Cavenee WK . 1993 J Clin Invest 91: 3

  • Chang WY, Cairns P, Schoenberg MP, Polascik TJ and Sidransky D . 1995 Cancer Res 55: 3246–3249.

  • Cheng M, Olivier P, Diehl JA, Fero M, Roussel MF, Roberts JM and Sherr CJ . 1999 EMBO J 18: 1571–1583.

  • Clurman B and Groudine M . 1997 Nature 389: 122–123.

  • Conn IG, Vilela MJ, Garrod DR, Crocker J and Wallace DM . 1990 Br J Urol 65: 176–180.

  • Davies G, Jiang WG and Mason MD . 1998 Oncol Rep 5: 1567–1576.

  • Degen WG, Agterbos MA, Muyrers JP, Bloemers HP and Swart GW . 1999 Biochim Biophys Acta 1444: 384–394.

  • Doki Y, Imoto M, Han EK, Sgambato A and Weinstein IB . 1997 Carcinogenesis 18: 1139–1148.

  • Emig R, Magener A, Ehemann V, Meyer A, Stilgenbauer F, Volkmann M, Wallwiener D and Sinn HP . 1998 Br J Cancer 78: 1661–1668.

  • Ewing CM, Ru N, Morton RA, Robinson JC, Wheelock MJ, Johnson KR, Barrett JC and Isaacs WB . 1995 Cancer Res 55: 4813–4817.

  • Fearon ER . 1997 Science 278: 1043–1050.

  • Garrod D, Chidgey M and North A . 1996 Curr Opin Cell Biol 8: 670–678.

  • Garrod DR . 1995 Cancer Surv 24: 97–111.

  • Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A and Reeve AE . 1998 Nature 392: 402–405.

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

  • Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S, Samid D, Duan DS, Gnarra JR, Linehan WM, et al. 1994 Proc Natl Acad Sci USA 91: 9700–9704.

  • Hirohashi S . 1998 Am J Pathol 153: 333–339.

  • Hoover KB, Liao SY and Bryant PJ . 1998 Am J Pathol 153: 1767–1773.

  • Hsieh JT, Luo W, Song W, Wang Y, Kleinerman DI, Van NT and Lin SH . 1995 Cancer Res 55: 190–197.

  • Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, Jessup JM and Kolodner R . 1997 Cancer Res 57: 808–811.

  • Kashiwabara K, Oyama T, Sano T, Fukuda T and Nakajima T . 1998 Int J Cancer 79: 215–220.

  • Kaur J, Srivastava A and Ralhan R . 1998 Int J Cancer 79: 370–375.

  • Kirkpatrick C and Peifer M . 1995 Curr Opin Genet Dev 5: 56–65.

  • Levine AJ, Momand J and Finlay CA . 1991 Nature 351: 453–456.

  • Lichter P and Cremer T . 1992 Human Cytogenetics a practical approach Oxford University Press.

    Google Scholar 

  • Marshall CJ, Franks LM and Carbonell AW . 1977 J Natl Cancer Inst 58: 1743–1751.

  • Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB and Sidransky D . 1995 Nat Med 1: 686–692.

  • Mitelman F, Mertens F and Johansson B . 1997 Nat Genet 15: 417–474.

  • Mutirangura A, Pornthanakasem W, Sriuranpong V, Supiyaphun P and Voravud N . 1998 Int J Cancer 78: 153–156.

  • Ouyang P . 1999 Biochem Biophys Res Commun 263: 192–200.

  • Ouyang P and Sugrue SP . 1992 J Cell Biol 18: 1477–1488.

  • Ouyang P and Sugrue SP . 1996 J Cell Biol 135: 1027–1042.

  • Perl AK, Wilgenbus P, Dahl U, Semb H and Christofori G . 1998 Nature 392: 190–193.

  • Shapiro GI, Edwards CD, Kobzik L, Godleski J, Richards W, Sugarbaker DJ and Rollins BJ . 1995 Cancer Res 55: 505–509.

  • Shi Y, Tabesh M, Shi J and Sugrue SP . 1997 Mol Biol Cell 8: 418a

  • Shiozaki H, Oka H, Inoue M, Tamura S and Monden M . 1996 Cancer 77: 1605–1613

  • Simcha I, Geiger B, Yehuda-Levenberg S, Salomon D and Ben-Ze'ev A . 1996 J Cell Biol 133: 199–209.

  • Taverna D, Ullman-Cullere M, Rayburn H, Bronson RT and Hynes RO . 1998 Cancer Res 58: 848–853.

  • Tlsty TD . 1998 Curr Opin Cell Biol 10: 647–653.

  • Tselepis C, Chidgey M, North A and Garrod D . 1998 Proc Natl Acad Sci USA 95: 8064–8069.

  • Warneford S, Townsend M, Rowe PB, Dalla-Pozza L and Symonds G . 1991 Cell Growth Differ 2: 439–445.

  • Weaver DA, Hei TK, Hukku B, McRaven JA and Willey JC . 1997 Carcinogenesis 18: 1251–1257.

  • Yokomizo A, Mai M, Tindall DJ, Cheng L, Bostwick DG, Naito S, Smith DI and Liu W . 1999 Oncogene 18: 1629–1633.

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Acknowledgements

We thank Dr Nick Muzyczka for the pindGFP construct, Mohammad Tabesh, Summer Carter and Michael Rutenberg for technical assistance, and Todd Barnash for graphic assistance. We also thank Matthew N. Simmons for assistance in the manuscript revision. Work supported by National Institutes of Health grant EY07883.

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  1. Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, 32610-0235, Florida, FL, USA

    Yujiang Shi & Stephen P Sugrue

  2. Chang Gung University Medical College, Tau-Yuan, Taiwan, Republic of China

    Pin Ouyang

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Shi, Y., Ouyang, P. & Sugrue, S. Characterization of the gene encoding pinin/DRS/memA and evidence for its potential tumor suppressor function. Oncogene 19, 289–297 (2000). https://doi.org/10.1038/sj.onc.1203328

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