MDA-MB-453, AN ANDROGEN-RESPONSIVE HUMAN BREAST-CARCINOMA CELL-LINE WITH HIGH-LEVEL ANDROGEN RECEPTOR EXPRESSION

The role of androgens and the androgen receptor (AR) in the developmen t and progression of breast cancer is poorly understood. To further de fine a potential model for androgen action in breast cancer, MDA-MB-45 3 cells, which express AR in the absence of oestrogen receptors and pr ogesterone receptors, were further characterised in terms of AR expres sion and androgen responsiveness. High level expression of AR was conf irmed by northern blot analysis, radioligand binding and immunocytoche mistry, and could not be accounted for by AR gene amplification. Three endogenous androgen-responsive genes (fatty acid synthetase, gross cy stic disease fluid protein of 15 kDa and prolactin receptor) and a tra nsfected reporter gene, containing an androgen-responsive element, wer e induced following androgen administration. A synthetic androgen, mib olerone, induced moderate (27% above control) stimulation of MDA-MB-45 3 cell proliferation, which was abrogated by the simultaneous administ ration of the synthetic androgen antagonist, anandron, demonstrating t hat the effect was AR-mediated. In summary, MDA-MB-453 cells express h igh levels of functional AR, and thus provide a valuable in vitro mode l for further studies on androgen regulation of gene expression, and p erhaps cell proliferation in breast cancer.