Par-4 deficiency cooperates with PTEN haploinsufficiency in prostate cancer initiation and progression and their simultaneous inactivation, in addition to enhancing Akt activation, sets in motion a unique mechanism involving the synergistic activation of NFkappaB.
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.
This review discusses salient features of molecules such as, Bcl-2, Bcl-(XL), NF-kappaB, Akt, PTEN and Par-4 that play a significant role in the regulation of prostate cancer and focuses on the prospects of effectively utilizing their potential for the therapy of hormone-sensitive and hormone-resistant prostate cancer.
These results establish the cooperation between Par-4 and PTEN as relevant for the development of prostate cancer and implicate the NF-kappaB pathway as a critical event in prostate tumorigenesis.