Androgen receptor and caveolin-1 in prostate cancer.
The androgen receptor (AR) is involved in the development and maintenance of the normal prostate and the development and progression of prostate cancer (PCa). Caveolin-1 (cav-1) is an AR co-regulator. The expression of this integral membrane protein is upregulated in PCa and correlates positively with its development. This review focuses on the likely interactive roles of AR and cav-1, with particular reference to progression to androgen-insensitivity in PCa. The classical role of AR is modulation of gene transcription by binding specific DNA sequences called androgen response elements in the promoter regions of target genes. To carry out this role, AR interacts with many co-regulator proteins which either enhance or repress its activation. Altered expression or misregulated activation of a co-regulator protein may significantly alter AR activity and the basal transcription rate of androgen responsive genes. Cav-1 has roles in cell signalling and trafficking, roles that are important in PCa survival, metastasis, and the development of multidrug resistant phenotypes. Although cav-1 appears to increase AR genomic activity and increase tumor cell survival, there is also mounting evidence that cav-1 can manipulate rapid, non-genomic AR signalling at the plasma membrane. By increasing our understanding of cav-1 as an AR co-regulator, we may be able to reinstate appropriate transcriptional responses to androgen signalling and minimise misregulated AR activity, thus permitting more effective targeted therapies for PCa.
Bennett
Nigel
N
UQCCR, School of Medicine, Faculty of Health Sciences, University of Queensland, Brisbane, QL, Australia.
Hooper
John D
JD
Lee
C Soon
CS
Gobe
Glenda C
GC
D051242:Caveolin 1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*
D051242:Caveolin 1; D011944:Receptors, Androgen