Androgen receptor mediated growth control of breast cancer and endometrial cancer modulated by antiandrogen- and androgen-like steroids

Androgens are involved in many regulatory processes in mammary and endometrial epithelium, but their role in the development and progression of breast and endometrial carcinoma is poorly understood. Androgen receptors (AR) are found in normal epithelium as well as in more than 50% of specimen from both tumor types. The occurrence of AR is correlated with estrogen and progesterone receptors. Androgen receptor positive cell lines were established during the last few years in our laboratory from malignant mammary (MFM-223) and endometrial (MFE-296) tumors supplementing the small number of androgen-responsive cell lines published so far. In this paper some aspects of the role of androgens in these two types of hormone responsive female cancer are presented. The proliferation of ZR-75-1, MFM-223 and MFE-296 cells is inhibited by androgens. The progestin medroxyprogesterone acetate inhibits the proliferation of estrogen- and progesterone receptor negative MFM-223 cells via the androgen receptor. Some steroid metabolites with distinct estrogenic properties like androst-5-ene-3 beta,17 beta-diol possess androgenic properties in this model system. Androgens stimulate the in vitro secretion of gross cystic disease fluid proteins by human mammary cancer cells. These proteins are normally found in benign breast cysts in vivo. The occurrence of gross cystic disease is correlated with an increased risk of breast cancer. The AR is autoregulated in MFM-223 mammary cancer cells on the protein and mRNA level. In MFE-296 cells with endometrial origin AR protein was increased after incubation with androgens.