CHARACTERIZATION OF THE ESTROGEN-RECEPTOR TRANSFECTED MCF10A BREAST CELL-LINE 139B6

There has been increasing evidence which suggests that abnormal expres sion of the estrogen receptor (ER) protein in nonmalignant breast tiss ue may be important in the carcinogenic process. To examine the effect s of ER expression in immortalized nonmalignant mammary epithelial cel ls, an expression vector containing human ER cDNA was transfected into the ER negative human breast cells, MCF10A. Characterization of a clo ne stably expressing ER, 139B6, provided evidence for the regulated sy nthesis of a functional ER capable of binding estradiol-17 beta (E(2)) and undergoing processing. Expression of the ER gene did not enable E (2) to stimulate endogenous genes [progesterone receptor (PgR), pS2, c athepsin D and TGF alpha] which normally respond to estrogens in breas t cancer cells. The ER in 139B6 cells was, however, capable of inducin g expression of an ERE-regulated reporter gene, indicating its ability to interact with transcriptional machinery. Furthermore, cultures in log growth displayed a slight increase in doubling time in the presenc e of E(2). These results indicate that ER expression alone is not suff icient to induce a transformed phenotype. Thus, the 139B6 cell line sh ould provide a new model for determining what additional changes lead to increased growth potential in response to E(2) and for exploring ho w E(2) itself may help bring about changes leading to progression of p reneoplastic breast epithelial cells.