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 language | English |
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Pages (from-to) | 623-631 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 18 |
Issue number | 3 |
DOIs | |
State | Published - 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