Expression, structure, and function of androgen receptor in advanced prostatic carcinoma.
BACKGROUND
Endocrine therapy for prostate cancer aims to reduce the levels of circulating androgen or to inhibit androgen action by blocking the androgen receptor in the prostate, or both. Studies in various animal and human prostate cancer models suggested that there may be a downregulation of androgen receptor during prostate cancer progression. Recent work, however, showed androgen receptor expression in all stages of prostate cancer. The presence of mutant androgen receptors in a portion of prostate cancers and receptor activation in the absence of androgen or in the presence of low androgen concentrations is discussed within this context.


METHODS
This review attempts to summarize the literature on androgen receptor expression in vitro and in vivo, as well as structural and functional alterations and communication between androgen signal transduction cascade and other signaling pathways.


CONCLUSIONS
Prostate tumors adapt to an environment with low androgen supply by using a hyperactive androgen receptor. The mechanisms involved are mutations of the androgen receptor generating receptors with broadened activation spectrum, increased receptor expression, and activation by interaction with other signaling pathways.
Culig
Z
Z
Department of Urology, University of Innsbruck, Austria.
Hobisch
A
A
Hittmair
A
A
Peterziel
H
H
Cato
A C
AC
Bartsch
G
G
Klocker
H
H
D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
D000726:Androgen Antagonists; D000728:Androgens; D011944:Receptors, Androgen