Growth inhibition and growth stimulation by estradiol of estrogen receptortransfected human breast epithelial cell lines involve different pathways

Epidermal growth factor (EGF) and estradiol (E2) are important mitogens in breast epithelial cells, and expression of epidermal growth factor receptor (EGFR) and estrogen receptor (ER) is often inversely correlated in human b reast cancer cells. Stable transfection of ER-negative cells with ER cDNA i s not sufficient to restore E2-mediated growth stimulation, on the contrary , E2 often inhibits growth of ER-transfected cell lines. In this study we u sed the ER-transfected human breast epithelial cell lines HMT-3522F9, growt h inhibited by E2 in the presence of EGF, and HMT-3522F9/S3B, growth stimul ated by E2 in the absence of EGF. In S3B cells, no active MAP kinase could be detected in response to E2, suggesting that signalling through the MAP k inase is not the major pathway in the E2-mediated growth stimulation. Inter estingly, a decreased level of active MAP kinase was observed in HMT-3522F9 cells in response to E2, indicating that in these cells cross-talk between the ER and the MAP kinase signalling pathway could be due to the E2-mediat ed growth inhibition. Moreover, we found that EGF-induced signalling also c ould be reduced by E2 in S3B cells, suggesting a general mechanism of actio n by E2 in cells concomitantly expressing ER and EGFR.