Abstract:
:The last decade has brought increased awareness to prostate cancer as a significant health problem. Prostate cancer is very heterogeneous in its etiology and progression, but androgen signaling appears to be a common key element in its development and progression. Blocking of androgen signaling results in a decrease in tumor volume as well as a decline in serum PSA in the majority of patients with prostate cancer. Today, endocrine therapy involves androgen depletion by orchiectomy or by treatment with LHRH-analoga as well as blockade of the androgen receptor (AR) with anti-androgens. However, during these treatments almost all tumors relapse to a hormone-insensitive state. The mechanisms that lead from initially androgen-sensitive to androgen-unresponsive tumor cell growth have been partly elucidated by new insights into the molecular mechanisms of androgen receptor signaling over the past several years. In addition to androgen receptor mutations that broaden the ligand-specificity of the AR, androgen-independent transactivation of the AR by peptide growth factors such as epidermal growth factor and insulin-like growth factor-I has been discovered. Furthermore, analysis of proteins that interact with the AR led to the isolation of coactivator proteins that mediate transcriptional activation by the AR. The following review will discuss the elements involved in androgen receptor signaling and summarize the present knowledge of their biological and clinical relevance in advanced prostate cancer.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Cronauer MV,Schulz WA,Burchardt T,Anastasiadis AG,de la Taille A,Ackermann R,Burchardt Mdoi
10.3892/ijo.23.4.1095keywords:
subject
Has Abstractpub_date
2003-10-01 00:00:00pages
1095-102issue
4eissn
1019-6439issn
1791-2423journal_volume
23pub_type
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