Impaired retinoic acid (RA) signal leads to RARbeta2 epigenetic silencing and RA resistance.

ABSTRACT: Resistance to the growth-inhibitory action of retinoic acid (RA), the bioactive derivative of vitamin A, is common in human tumors. One form of RA resistance has been associated with silencing and hypermethylation of the retinoic acid receptor beta2 gene (RARbeta2), an RA-regulated tumor suppressor gene. The presence of an epigenetically silent RARbeta2 correlates with lack of the RA receptor alpha (RARalpha). Normally, RARalpha regulates RARbeta2 transcription by mediating dynamic changes of RARbeta2 chromatin in the presence and absence of RA. Here we show that interfering with RA signal through RARalpha (which was achieved by use of a dominant-negative RARalpha, by downregulation of RARalpha by RNA interference, and by use of RARalpha antagonists) induces an exacerbation of the represse

SUBMITTER: Ren M 

PROVIDER: S-EPMC1291229 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature