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Expression, structure, and function of androgen receptor in advanced prostatic carcinoma
Z Culig1, A Hobisch, A Hittmair
1Department of Urology, University of Innsbruck, Austria.
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.
Insights
Prostate tumors adapt to low androgen conditions by developing a hyperactive androgen receptor. This involves mutations, increased expression, and cross-talk with other signaling pathways for cancer progression.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Endocrine therapy for prostate cancer targets androgen levels or androgen receptor (AR) action.
- While AR downregulation was suspected, AR is expressed across all prostate cancer stages.
- Mutant ARs and AR activation under low androgen conditions are critical factors.
Purpose of the Study:
- To review current literature on androgen receptor expression in prostate cancer.
- To explore structural and functional alterations of the AR.
- To examine AR signaling pathway interactions with other cellular pathways.
Main Methods:
- Literature review of in vitro and in vivo studies.
- Analysis of structural and functional AR alterations.
- Investigation of AR signaling pathway crosstalk.
Main Results:
- Prostate tumors exhibit AR hyperactivity in low androgen environments.
- Mechanisms include AR mutations leading to broader activation spectra.
- Increased AR expression and activation via other signaling pathways are observed.
Conclusions:
- Prostate cancer adapts to androgen deprivation through AR hyperactivity.
- Mutations, amplified expression, and pathway interactions enable tumor survival and progression.
- Understanding these adaptive mechanisms is key for future therapies.