Growth response of breast epithelial cells to estrogen is influenced by EGF

Estrogen-induced growth stimulation has not previously been demonstrated in estrogen receptor (ER) cDNA transfected human cell lines in contrast to breast cancer cell lines expressing endogenous ER. On the contrary, estrogen usually inhibits cell growth of ER transfected cell lines. Growth inhibition by estrogen has also been demonstrated in our cell line, F9, which is an ER transfected subline of HMT-3522 breast epithelial cells derived from fibrocystic disease and propagated in chemically defined medium. By omitting EGF in the medium, we have demonstrated not only an increased transcriptional activity of the ER but also--after an adaptation period--estrogen-dependent growth of the cells, and we have succeeded in establishing a new subline, S3B, that requires 17beta-estradiol (E2) for growth. This is the first example of a nonmalignant, human breast epithelial cell line which is dependent on estrogen for continued growth. The S3B cells express functional ER as measured by transcriptional activity. ER-E2 induced transcription was not inhibited by EGF as in F9 cells. We propose that a growth-stimulatory response of breast epithelial cells in vitro to E2 is dependent on an inactive or down-regulated EGF receptor signaling pathway and it is possible that the effect of estrogen on normal breast epithelium in vivo also is modulated by the EGFR.