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Mutually exclusive expression patterns of Bcl-2 and Par-4 in human prostate tumors consistent with down-regulation of Bcl-2 by Par-4

Oncogene volume 18, pages 623–631 (1999)Cite this article

Abstract

Par-4 is a widely expressed protein that sensitizes both prostatic and non-prostatic cells to apoptosis. Constitutive- or regulated- overexpression of Par-4 caused a reduction in the levels of the anti-apoptotic protein Bcl-2. Replenishment of Bcl-2 levels abrogated susceptibility to Par-4-dependent apoptosis, suggesting that Par-4-mediated apoptosis requires downmodulation of Bcl-2 levels. The inverse correlation between Par-4 and Bcl-2 expression was recapitulated in human prostate tumors. Par-4 but not Bcl-2 was detected in the secretory epithelium of benign prostatic tumors and in primary and metastatic prostate cancers that are apt to undergo apoptosis. Moreover, xenografts of human, androgen-dependent CWR22 tumors showed Par-4 but not Bcl-2 expression. By contrast, androgen-independent CWR22R tumors derived from the CWR22 xenografts showed mutually exclusive expression patterns of Par-4 and Bcl-2. These findings suggest a mechanism by which Par-4 may sensitize prostate tumor cells to apoptosis.

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Acknowledgements

This work was supported by NIH Grant CA60872, CaPCURE Award, and the Council for Tobacco Research-USA, Grant 3490 to VMR.

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Authors and Affiliations

  1. Department of Surgery, Division of Urology, University of Kentucky, Lexington, 40536, Kentucky, USA

    Guofang Qiu, Stephen F Sells & Vivek M Rangnekar

  2. Department of Radiation Medicine, University of Kentucky, Lexington, 40536, Kentucky, USA

    Mansoor Ahmed & Mohammed Mohiuddin

  3. Department of Pathology, University of Kentucky, Lexington, 40536, Kentucky, USA

    Michael H Weinstein

  4. Department of Microbiology & Immunology, University of Kentucky, Lexington, 40536, Kentucky, USA

    Vivek M Rangnekar

  5. LP Markey Cancer Center, University of Kentucky, Lexington, 40536, Kentucky, USA

    Mansoor Ahmed, Mohammed Mohiuddin, Michael H Weinstein & Vivek M Rangnekar

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  1. Guofang Qiu
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Qiu, G., Ahmed, M., Sells, S. et al. Mutually exclusive expression patterns of Bcl-2 and Par-4 in human prostate tumors consistent with down-regulation of Bcl-2 by Par-4. Oncogene 18, 623–631 (1999). https://doi.org/10.1038/sj.onc.1202344

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