ANDROGEN RECEPTOR-MEDIATED GROWTH-CONTROL OF BREAST-CANCER AND ENDOMETRIAL CANCER MODULATED BY ANTIANDROGEN-LIKE AND ANDROGEN-LIKE STEROIDS

Androgens are involved in many regulatory processes in mammary and end ometrial epithelium, but their role in the development and progression of breast and endometrial carcinoma is poorly understood. Androgen re ceptors (AR) are found in normal epithelium as well as in more than 50 % of specimen from both tumor types. The occurrence of AR is correlate d with estrogen and progesterone receptors. Androgen receptor positive cell lines were established during the last few years in our laborato ry from malignant mammary (MFM-223) and endometrial (MFE-296) tumors s upplementing the small number of androgen-responsive cell lines publis hed so far. In this paper some aspects of the role of androgens in the se two types of hormone responsive female cancer are presented. The pr oliferation of ZR-75-1, MFM-223 and MFE-296 cells is inhibited by andr ogens. The progestin medroxyprogesterone acetate inhibits the prolifer ation of estrogen- and progesterone receptor negative MFM-223 cells vi a the androgen receptor. Some steroid metabolites with distinct estrog enic properties like androst-5-ene-3 beta,17 beta-diol possess androge nic properties in this model system. Androgens stimulate the in vitro secretion of gross cystic disease fluid proteins by human mammary canc er cells. These proteins are normally found in benign breast cysts in vivo. The occurrence of gross cystic disease is correlated with an inc reased risk of breast cancer. The AR is autoregulated in MFM-223 mamma ry cancer cells on the protein and mRNA level. In MFE-296 cells with e ndometrial origin AR protein was increased after incubation with andro gens.