Androgen receptor amplification is associated with increased cell proliferation in prostate cancer.

Mechanisms of prostate cancer progression during hormonal therapy and the pathobiologic consequences of androgen receptor (AR) gene amplification are inadequately known. To further investigate the hypothesis that AR gene amplification is associated with increased cell proliferation, we analyzed 123 paraffin-embedded prostate cancer specimens from men who experienced tumor relapse during androgen withdrawal therapy. We used fluorescence in situ hybridization to quantify AR gene copy number and Ki-67 immunohistochemistry to determine cell proliferation.

Kruppel-like factor 6 germ-line mutations are infrequent in Finnish hereditary prostate cancer.

Purpose: Recently, Kruppel-like factor 6 gene (KLF6) has been shown to be inactivated in up to 77% of prostate carcinomas. KLF6 has an important role in regulating cell growth and differentiation. The function and high mutation frequency in sporadic prostate carcinomas make KLF6 an attractive candidate for prostate cancer predisposition and, therefore, DNA samples from 69 Finnish prostate cancer families were analyzed for KLF6 mutations.

Androgen receptor mutations in high-grade prostate cancer before hormonal therapy.

Androgen action is mediated through androgen receptor (AR), which appears to undergo structural and functional alterations during prostate cancer (CaP) progression. AR mutations have been infrequently reported in CaP before hormonal therapy, but in untreated, advanced tumors AR mutations are suggested to be more common. To investigate the frequency of AR mutations in aggressive CaP before hormonal therapy, we have analyzed AR coding region for aberrations in 21 paraffin-embedded prostate carcinoma samples (14 primary tumors, 7 metastases) of poor histologic differentiation.

Germline mutation analysis of the androgen receptor gene in Finnish patients with prostate cancer.

Purpose: Steroid hormones, particularly androgens, are suspected to have a major role in prostate carcinogenesis. Since androgen receptor mediates androgenic effects on cells and recent studies suggest that the androgen receptor gene is a putative prostate cancer susceptibility locus, we screened the coding region of the androgen receptor gene for germline mutations using the genomic DNA of patients with prostate cancer.

Materials And Methods: DNA samples from 38 patients with early onset prostate cancer and 36 from Finnish prostate cancer families showing no male-to-male transmission of prostate cancer were analyzed for mutations in the androgen receptor gene using single strand conformation polymorphism analysis and subsequent sequencing.