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

Guofang Qiu, Mansoor Ahmed, Stephen F. Sells, Mohammed Mohiuddin, Michael H. Weinstein, Vivek M. Rangnekar

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

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.

Original languageEnglish
Pages (from-to)623-631
Number of pages9
JournalOncogene
Volume18
Issue number3
DOIs
StatePublished - Jan 21 1999

Bibliographical note

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

Keywords

  • Apoptosis
  • Bcl-2
  • Par-4
  • Prostate

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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