Quantitation of androgen receptor gene expression in sporadic breast tumors by real-time RT-PCR: Evidence that MYC is an AR-regulated gene

Abstract

Little is known of the function and clinical significance of the androgen receptor (AR) in human breast cancer. Paradoxically, synthetic progestins, such as medroxy-progesterone acetate, are used for second line hormone therapy of breast cancer following tamoxifen failure. A sensitive and accurate assay for AR expression in breast tumors is thus required. Here we have developed and validated a real-time RT-PCR assay to quantify AR gene expression at the mRNA level in a series of 131 patients with unilateral invasive primary breast tumors. AR expression varied widely in tumor tissues (by at least 3 orders of magnitude), being underexpressed in 24/131 (18.3%) and overexpressed in 45/131 (34.4%) relative to normal breast tissues. We observed links (or trends) between AR status and age, menopausal status, Scarff-Bloom-Richardson histopathological grade, lymph node status and estrogen receptor α and progesterone receptor status. High AR mRNA levels were negatively linked to MYC gene over-expression (P = 8 × 10-6), confirming previous in vitro studies. Our results also suggest a role of the ARA70 gene (which encodes a major AR co-activator) in the AR pathway dysregulation observed in breast cancer. This simple, rapid and semi-automated method will be useful for screening cancer patients for altered AR expression and for predicting the response to androgen therapy in AR-related cancer patients.