Prostate cancer progression to androgen independence - do changes in the androgen receptor CAG repeat number play a role?

Abstract

Prostate cancer is the commonest non-cutaneous male malignancy and is the second commonest cause of cancer-related deaths in many Western countries. Approximately half of all men diagnosed with prostate cancer will have incurable advanced disease. Most of these men are treated with and initially respond to androgen-ablative therapy. However, the duration of response is variable, and most patients will eventually progress to androgen-independent disease. The mechanisms that drive prostate cancer progression are not clear, although the androgen receptor appears to play a key role. The androgen receptor gene contains polymorphic CAG and GGC trinucleotide repeats. CAG repeat length has been inversely correlated with prostate cancer risk and androgen receptor transcriptional activity. This study aimed to examine the role of the CAG repeat in prostate cancer progression to androgen-independence. This study firstly examined the CAG repeat number in a range of tumorogenic and non-tumorogenic prostate cell lines. In particular, the study compared the CAG repeat number of the androgen-dependent LNCaP cell line with that of the androgen-independent sub-line of LNCaP, the LNCaP-HOF cell line.