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Bcl-2 accelerates multistep prostate carcinogenesis in vivo

Abstract

The impact of bcl-2 proto-oncogene expression on the pathogenesis and progression of prostate cancer was examined in a transgenic mouse model. Probasin-bcl-2 transgenic mice were crossed with TRAMP (TRansgenic Adenocarcinoma Mouse Prostate) mice that express the SV40 early genes (T/t antigens) under probasin control. Prostate size, cell proliferation, apoptosis, and the incidence and latency of tumor formation were evaluated. The double transgenic, probasin-bcl-2 X TRAMP F1 (BxT) mice exhibited an increase in the wet weight of the prostate. This was associated with an increase in proliferation, attributable to T/t antigens, and a decrease in apoptosis attributable to bcl-2. The latency to tumor formation was also decreased in the BxT mice compared to the TRAMP mice. The incidence of metastases was identical in both the TRAMP and BxT mice. Lastly, the incidence of hormone-independent prostate cancer was reduced in the BxT mice compared to the TRAMP mice. Together, these results demonstrate that bcl-2 can facilitate multistep prostate carcinogenesis in vivo.

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References

  • Bauer JJ, Sesterhenn IA, Mostofi FK, McLeod DG, Srivastava S and Moul JW. . 1995 Clin. Cancer Res. 1: 1295–1300.

  • Beham AW, Sarkiss M, Brisbay S, Tu S-M, von Eschenbach AC and McDonnell TJ. . 1998 Int. J. Mol. Med. 1: 953–959.

  • Berner A, Nesland JM, Waehre H, Silde J and Fossa SD. . 1993 Br. J. Cancer 68: 380–384.

  • Bookstein R, Rio P, Madreperla SA, Hong F, Alred C, Grizzle WE and Lee WH. . 1990 Proc. Natl. Acad. Sci, USA 87: 7762–7766.

  • Bruckheimer EM, Cho SH, Johnson D, Gingrich JR, Greenberg NM and McDonnell TJ. . 2000 Oncogene 19: 2404–2412.

  • Colombel M, Symmans F, Gil S, O'Toole KM, Chopin D, Benson M, Olsson CA, Korsmeyer S and Buttyan R. . 1993 Am. J. Pathol. 143: 390–400.

  • Damania B and Alwine JC. . 1996 Genes Dev. 10: 1369–1381.

  • DeCaprio JA, Ludlow JW, Figge J, Shew JY, Huang CM, Lee WH, Marsilio E, Paucha E and Livingston DM. . 1988 Cell 54: 275–283.

  • Eng MH, Charles LG, Ross BD, Chrisp CE, Pienta KJ, Greenberg NM, Hsu CX and Sanda MG. . 1999 Urology 54: 1112–1119.

  • Gavrieli Y, Sherman Y and Ben-Sasson SA. . 1992 J. Cell. Biol. 119: 493–501.

  • Gingrich JR, Barrios RJ, Morton RA, Boyce BF, DeMayo FJ, Finegold MJ, Angelopoulou R, Rosen JM and Greenberg NM. . 1996 Cancer Res. 56: 4096–4102.

  • Gingrich JR, Barrios RJ, Kattan MW, Nahm HS, Finegold MJ and Greenberg NM. . 1997 Cancer Res. 57: 4687–4691.

  • Gingrich JR, Barrios RJ, Foster BA and Greenberg NM. . 1999 Pros. Cancer Pros. Dis. 2: 70–75.

  • Greenberg NM, DeMayo F, Finegold MJ, Medina D, Tilley WD, Aspinall JO, Cunha GR, Donjacour AA, Matusik RJ and Rosen JM. . 1995 Proc. Natl. Acad. Sci. USA. 92: 3439–3443.

  • Greenberg NM, DeMayo FJ, Shepard PC, Barrios R, Lebovitz R, Finegold M, Angelpoulou R, Dodd JG, Duckworth ML and Rosen JM. . 1994 Mol. Endocrinol. 8: 230–239.

  • Heidenberg HB, Bauer JJ, McLeod DG, Moul JW and Srivastava S. . 1996 Urology 48: 971–979.

  • Hsu CX, Ross BD, Chrisp CE, Derrow SZ, Charles LG, Pienta KJ, Greenberg NM, Zeng Z and Sanda MG. . 1998 J. Urol. 160: 1500–1505.

  • Johnson MI and Hamdy FC. . 1998 Oncol. Reports 5: 553–557.

  • Keshgegian AA, Johnston E and Cnaan A. . 1998 Am. J. Clin. Pathol. 110: 443–449.

  • Landis SH, Murray T, Bolden S and Wingo PA. . 1999 CA Cancer J. Clin. 49: 8–31.

  • Lane DP and Crawford LV. . 1979 Nature 278: 261–263.

  • Linzer DI, Maltzman W and Levine AJ. . 1979 Virology 98: 308–318.

  • Mateer SC, Federov SA and Mumby MC. . 1998 J. Biol. Chem. 273: 35339–35346.

  • May E, Breugnot C, Duthu A and May P. . 1991 Virology 180: 285–293.

  • McDonnell TJ. . 1993 Molec. Carcinogen. 8: 209–213.

  • McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LW, Hsieh JT, Tu SM and Campbell ML. . 1992 Cancer Res. 52: 6940–6944.

  • Pettaway CA. . 1998 Techniques Urol. 4: 35–42.

  • Raffo AJ, Perlkman H, Chen MW, Day ML, Streitman JS and Buttyan R. . 1995 Cancer Res. 55: 4438–4445.

  • Rubin SJ, Hallahan DE, Ashman CR, Brachman DG, Beckett MA, Virudachalam S, Yandell DW and Rutter WJ. . 1991 J. Surg. Oncol. 46: 31–36.

  • Sullivan GF, Amenta PS, Villanueva JD, Alvarez CJ, Yang JM and Hait WN. . 1998 Clin. Cancer Res. 4: 1393–1403.

  • Thomas DJ, Robinson M. King P, Hasan T, Charlton RP, Martin J, Carr TW and Neal DE. . 1993 Br. J. Urol. 72: 778–781.

  • Westin P, Lo P, Marin CM, Fernandez A, Sarkiss M, Tu S-M, Brisbay SM, von Eschenbach AC and McDonnell TJ. . 1997 Int. J. Oncol. 10: 113–118.

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Acknowledgements

This work was supported by a grant from the American Cancer Society (RPG-96-036-04-CDD), an award from CaP CURE (The Association for the Cure of Cancer of the Prostate), NIH CA58204 (to NM Greenberg), and NIH Training Grant T32 CA67759-01 (EM Bruckheimer).

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Bruckheimer, E., Brisbay, S., Johnson, D. et al. Bcl-2 accelerates multistep prostate carcinogenesis in vivo. Oncogene 19, 5251–5258 (2000). https://doi.org/10.1038/sj.onc.1203881

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