Growth inhibition and growth stimulation by estradiol of estrogen receptor transfected 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 breast cancer cells. Stable transfection of ER-negative cells with ER cDNA is not sufficient to restore E2-mediated growth stimulation, on the contrary, E2 often inhibits growth of ER-transfected cell lines. In this study we used the ER-transfected human breast epithelial cell lines HMT-3522F9, growth inhibited by E2 in the presence of EGF, and HMT-3522F9/S3B, growth stimulated 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 kinase is not the major pathway in the E2-mediated growth stimulation. Interestingly, 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-mediated growth inhibition. Moreover, we found that EGF-induced signalling also could be reduced by E2 in S3B cells, suggesting a general mechanism of action by E2 in cells concomitantly expressing ER and EGFR.
Lundholt
B K
BK
Department of Tumor Endocrinology, Institute of Cancer Biology, Danish Cancer Society, Copenhagen.
Briand
P
P
Lykkesfeldt
A E
AE
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D018076:DNA, Complementary; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D011960:Receptors, Estrogen; D004958:Estradiol; D004815:Epidermal Growth Factor; D020928:Mitogen-Activated Protein Kinases