Target gene-specific regulation of androgen receptor activity by p42/p44 mitogen-activated protein kinase.

ABSTRACT: Evidence that the androgen receptor (AR) is not only important in androgen-dependent prostate cancer, but also continues to play a role in tumors that become resistant to androgen deprivation therapies, highlights the need to find alternate means to block AR activity. AR, a hormone-activated transcription factor, and its coactivators are phosphoproteins. Thus, we sought to determine whether inhibition of specific cell signaling pathways would reduce AR function. We found that short-term inhibition of p42/p44 MAPK activity either by a MAPK kinase inhibitor, U0126, or by depletion of kinase with small interfering RNA caused target gene-specific reductions in AR activity. AR enhances histone H3 acetylation of target genes that are sensitive to U0126 including prostate-specific antigen and TMP

SUBMITTER: Agoulnik IU 

PROVIDER: S-EPMC2582542 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature