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Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22

Oncogene volume 20, pages 4169–4179 (2001)Cite this article

Abstract

Deletions in the 8p21-22 region of the human genome are among the most common genetic alterations in prostate carcinomas. Several studies in different tumor tissues, including prostate, indicate that there are probably multiple tumor suppressor genes (TSGs) present in this region. To identify candidate TSGs on 8p22 a YAC contig spanning this region was assembled and YAC clones retrofitted with a selectable marker (neo) were transferred into rat prostate AT6.2 cells. Two overlapping YAC clones showed greatly reduced colony-forming efficiency, indicating they may carry a TSG. Two BAC clones encompassing the overlapping region also appeared to exert suppressive effects on the growth of AT6.2 cells. Database searches for genes mapped to the critical region identified a gene known as FEZ1 (LZTS1) as a potential candidate suppressor gene. Subsequent experiments showed that over-expression of LZTS1 cDNA inhibited stable colony-forming efficiencies of AT6.2, HEK-293 and LNCaP cells. In contrast, LZTS1-transfected Rat-1 and RM1 cells were growth-stimulated. Database searches also identified additional isoforms of the LZTS1 mRNA, as well as LZTS1 protein domains reminiscent of those found in transcription factors. Together these data suggest that the LZTS1 gene is involved in the regulation of cell growth and its loss of function may contribute to the development of prostatic carcinomas, as well as other cancers.

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References

  • Albertsen H, Abderrahim H, Cann HM, Dausset J, Le Paslier D, Cohen D . 1990 Proc. Natl. Acad. Sci. USA 87: 4256–4260

  • Allan LA, Duhig T, Read M, Fried M . 2000 Mol. Cell. Biol. 20: 1291–1298

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ . 1990 J. Mol. Biol. 215: 403–410

  • Anderson MJ, Stanbridge EJ . 1993 FASEB J. 7: 826–833

  • Baker A, Cotten M . 1997 Nucleic Acids Res. 25: 1950–1956

  • Baley PA, Yoshida K, Qian W, Sehgal I, Thompson TC . 1995 J. Steroid Biochem. Mol. Biol. 52: 403–413

  • Bellanne-Chantelot C, Lacroix B, Ougen P, Billault A, Beaufils S, Bertrand S, Georges I, Glibert F, Gros I, Lucotte G, Susini L, Codani J-J, Gesnoulin P, Pook S, Vaysseix G, Lu-Kuo J, Ried T, Ward D, Chumakov I, Le Paslier D, Barillot E, Cohen D . 1992 Cell 70: 1059–1068

  • Bhatia-Gaur R, Donjacour AA, Sciavolino PJ, Kim M, Desai N, Young P, Norton CR, Gridley T, Cardiff RD, Cunha GR, Abate-Shen C, Shen MM . 1999 Genes Dev. 13: 966–977

  • Bookstein R, Levy A, MacGrogan D, Lewis TB, Weissenbach J, O'Connell P, Leach RJ . 1994 Genomics 24: 317–323

  • Bova GS, MacGrogan D, Levy A, Pin SS, Bookstein R, Isaacs WB . 1996 Genomics 35: 46–54

  • Burgers PM, Percival KJ . 1987 Anal. Biochem. 163: 391–397

  • Cabeza-Arvelaiz Y, Shih LC, Hardman N, Asselbergs F, Bilbe G, Schmitz A, White B, Siciliano MJ, Lachman LB . 1993 DNA Cell Biol. 12: 881–892

  • Ceballos E, Delgado MD, Gutierrez P, Richard C, Muller D, Eilers M, Ehinger M, Gullberg U, Leon J . 2000 Oncogene 19: 2194–2204

  • Chinault AC . 1994 Current Protocols in Human Genetics, Vol. 1. Dracopoli, NC, Haines JL, Korf BR, Moir DJ, Morton CC, Seidman CE, Seidman, JG and Smith DR (eds) John Wiley and Sons, Inc.: New York pp. 5.5.1–5.5.10

  • Chiu R, Angel P, Karin M . 1989 Cell 59: 979–986

  • Chumakov IM, Rigault P, Le Gall I, Bellanne-Chantelot C, Billault A, Guillou S, Soularue P, Guasconi G, Poullier E, Gros I, Belova M, Sambucy JL, Susini L, Gervy P, Glibert F, Beaufils S, Bui H, Massart C, De Tand MF, Dukasz F, Lecoulant S, Ougen P, Perrot V, Saumier M, Sovarito C, Bahouayila R, Cohen-Akenine A, Lacroix B, Lucotte G, Sahbatou M, Schmit C, Sangouard M, Tubacher E, Dib C, Faure S, Fizames C, Gyapay G, Millasseau P, Nguyen S, Muselet D, Vignal A, Morissette J, Menninger J, Lieman J, Desai T, Banks A, Bray-Ward P, Ward D, Hudson T, Gerety S, Foote S, Stein L, Page DC, Lander ES, Weinssenbach J, le Paslier D, Cohen D . 1995 Nature 377: 175–297

  • Courey AJ, Tjian R . 1988 Cell 55: 887–898

  • Evan G, Littlewood T . 1998 Science 281: 1317–1322

  • Farrington SM, Cunningham C, Boyle SM, Wyllie AH, Dunlop MG . 1996 Oncogene 12: 1803–1808

  • Foulkes NS, Sassone-Corsi P . 1996 Biochim. Biophys. Acta 1288: F101–F121

  • Fujiwara Y, Ohata H, Kuroki T, Koyama K, Tsuchiya E, Monden M, Nakamura Y . 1995 Oncogene 10: 891–895

  • Gossen M, Bujard H . 1992 Proc. Natl. Acad. Sci. USA 89: 5547–5551

  • Goyette MC, Cho K, Fasching CL, Levy DB, Kinzler KW, Paraskeva C, Vogelstein B, Stanbridge EJ . 1992 Mol. Cell Biol. 12: 1387–1395

  • Habener JF . 1990 Mol. Endocrinol. 4: 1087–1094

  • Harris H, Miller OJ, Klein G, Worst P, Tachibana T . 1969 Nature 223: 363–368

  • Hutton FG, Turnell AS, Gallimore PH, Grand RJ . 2000 Oncogene 19: 452–462

  • Ichikawa T, Nihei N, Suzuki H, Oshimura M, Emi M, Nakamura Y, Hayata I, Isaacs JT, Shimazaki J . 1994 Cancer Res. 54: 2299–2302

  • Ishii H, Baffa R, Numata SI, Murakumo Y, Rattan S, Inoue H, Mori M, Fidanza V, Alder H, Croce CM . 1999 Proc. Natl. Acad. Sci. USA 96: 3928–3933

  • Johnson DG . 2000 Mol. Carcinog. 27: 151–157

  • Kagan J, Stein J, Babaian RJ, Joe YS, Pisters LL, Glassman AB, von Eschenbach AC, Troncoso P . 1995 Oncogene 11: 2121–2126

  • Kirschner LS, Stratakis CA . 1999 Biotechniques 27: 72–74

  • Koreth J, Bakkenist CJ, Larin Z, Hunt NCA, James MR, McGee JOD . 1999 Oncogene 18: 1157–1164

  • Laoide BM, Foulkes NS, Schlotter F, Sassone-Corsi P . 1993 EMBO J. 12: 1179–1191

  • Lu X, Park SH, Thompson TC, Lane DP . 1992 Cell 70: 153–161

  • Lucibello FC, Lowag C, Neuberg M, Muller R . 1989 Cell 59: 999–1007

  • MacGrogan D, Levy A, Bova GS, Isaacs WB, Bookstein R . 1996 Genomics 35: 55–65

  • Markie D, Ragoussis J, Senger G, Rowan A, Sansom D, Trowsdale J, Sheer D, Bodmer WF . 1993 Somat. Cell. Mol. Genet. 19: 161–169

  • Mitchell KO, El-Deiry WS . 1999 Cell Growth Differ. 10: 223–230

  • Molina CA, Foulkes NS, Lalli E, Sassone-Corsi P . 1993 Cell 75: 875–886

  • Morgenstern JP, Land H . 1990 Nucleic Acids Res. 18: 1068

  • Murakami Y, Nobukuni T, Tamura K, Maruyama T, Sekiya T, Arai Y, Gomyou H, Tanigami A, Ohki M, Cabin D, Frischmeyer P, Hunt P, Reeves RH . 1998 Proc. Natl. Acad. Sci. USA 95: 8153–8158

  • Murakami YS, Albertsen H, Brothman AR, Leach RJ, White RL . 1996 Cancer Res. 56: 2157–2160

  • Pachnis V, Pevny L, Rothstein R, Costantini F . 1990 Proc. Natl. Acad. Sci. USA 87: 5109–5113

  • Park BJ, Park JI, Byun DS, Park JH, Chi SG . 2000 Cancer Res. 60: 3031–3038

  • Pirrotta V, Manet E, Hardon E, Bickel SE, Benson M . 1987 EMBO J. 6: 791–799

  • Reddy DE, Keck CL, Popescus N, Athwal RS, Kaur GP . 2000 Oncogene 19: 217–222

  • Tsai SY, Sagami I, Wang H, Tsai MJ, O'Malley BW . 1987 Cell 50: 701–709

  • Tuck SP, Crawford L . 1989 Oncogene Res. 4: 81–96

  • Zeng YX, Somasundaram K, El-Deiry WS . 1997 Nat. Genet. 15: 78–82

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Acknowledgements

We thank Dr D Markie for providing the vector pRAN4 and for helpful suggestions, Dr M Cotten for providing the GFP BAC reporter vectors and helpful suggestions, Drs C Croce and H Ishii for the FEZ1 cDNA, Dr L Pastori for the adenovirus and Dr D Geng for assistance during the YAC structural analysis. This study was supported by NIH SPORE Grant P50-CA58204.

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Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 77030, Texas, TX, USA

    Yofre Cabeza-Arvelaiz & A Craig Chinault

  2. Department of Pathology, Baylor College of Medicine, Houston, 77030, Texas, TX, USA

    Jorge L Sepulveda & Russell M Lebovitz

  3. Department of Urology, Baylor College of Medicine, Houston, 77030, Texas, TX, USA

    Timothy C Thompson

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  1. Yofre Cabeza-Arvelaiz
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Correspondence to A Craig Chinault.

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Cabeza-Arvelaiz, Y., Sepulveda, J., Lebovitz, R. et al. Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22. Oncogene 20, 4169–4179 (2001). https://doi.org/10.1038/sj.onc.1204539

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