Mutually exclusive expression patterns of Bcl-2 and Par-4 in human prostate tumors consistent with down-regulation of Bcl-2 by Par-4
- PMID: 9989812
- DOI: 10.1038/sj.onc.1202344
Mutually exclusive expression patterns of Bcl-2 and Par-4 in human prostate tumors consistent with down-regulation of Bcl-2 by Par-4
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.
Similar articles
-
Ectopic expression of Par-4 leads to induction of apoptosis in CNS tumor cell lines.Int J Oncol. 2005 Jan;26(1):159-67. Int J Oncol. 2005. PMID: 15586236
-
In lymphatic cells par-4 sensitizes to apoptosis by down-regulating bcl-2 and promoting disruption of mitochondrial membrane potential and caspase activation.Cancer Res. 2002 Mar 15;62(6):1768-75. Cancer Res. 2002. PMID: 11912153
-
Par-4 inducible apoptosis in prostate cancer cells.J Cell Biochem. 2004 Feb 15;91(3):504-12. doi: 10.1002/jcb.20000. J Cell Biochem. 2004. PMID: 14755681 Review.
-
Suppression of prostate tumor cell growth in vivo by WT1, the Wilms' tumor suppressor gene.Int J Oncol. 2004 Mar;24(3):461-71. Int J Oncol. 2004. PMID: 14767530
-
Par-4 for molecular therapy of prostate cancer.Curr Drug Targets. 2003 Apr;4(3):223-30. doi: 10.2174/1389450033491163. Curr Drug Targets. 2003. PMID: 12643472 Review.
Cited by
-
Enhancing the Conformational Stability of the cl-Par-4 Tumor Suppressor via Site-Directed Mutagenesis.Biomolecules. 2023 Apr 12;13(4):667. doi: 10.3390/biom13040667. Biomolecules. 2023. PMID: 37189414 Free PMC article.
-
Antitumor Activity of Small Activating RNAs Induced PAWR Gene Activation in Human Bladder Cancer Cells.Int J Med Sci. 2021 Jun 16;18(13):3039-3049. doi: 10.7150/ijms.60399. eCollection 2021. Int J Med Sci. 2021. PMID: 34220332 Free PMC article.
-
Epigenetic Editing in Prostate Cancer: Challenges and Opportunities.Epigenetics. 2022 May;17(5):564-588. doi: 10.1080/15592294.2021.1939477. Epub 2021 Jun 15. Epigenetics. 2022. PMID: 34130596 Free PMC article. Review.
-
Prostate apoptosis response-4 and tumor suppression: it's not just about apoptosis anymore.Cell Death Dis. 2021 Jan 7;12(1):47. doi: 10.1038/s41419-020-03292-1. Cell Death Dis. 2021. PMID: 33414404 Free PMC article. Review.
-
Par-4 overexpression impedes leukemogenesis in the Eµ-TCL1 leukemia model through downregulation of NF-κB signaling.Blood Adv. 2019 Apr 23;3(8):1255-1266. doi: 10.1182/bloodadvances.2018025973. Blood Adv. 2019. PMID: 30987970 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical