Abstract
Transforming growth factor-α (TGF-α) contributes to the progression of mammary carcinogenesis in part through synergistic augmentation of estradiol (E2) action. To investigate this further, we sought to determine (1) whether the duration of TGF-α treatment might influence the nature of the TGF-α/E2 interaction, and (2) whether TGF-α would behave in a similar manner when combined with phytoestrogens. To this end, we transfected T47-D breast cancer cells with an estrogen-responsive reporter and then treated the cells (for 4–48 h) with varying concentrations of TGF-α, E2, the antiestrogen 4-hydroxy-tamoxifen (HOT), and/or one of three phytoestrogens. Our findings revealed that TGF-α has short-term synergistic and long-term inhibitory effects on E2-and phytoestrogen-regulated gene expression. Furthermore, this secondary inhibition of E2 action by TGF-α was similar in magnitude to that imposed by HOT. These findings demonstrate a novel role for TGF-α and invite reevaluation of current models regarding TGF-αs interactions with E2 inbreast cancer cells. Our results also raise the possibility that phytoestrogens, which interact with TGF-α in a manner conceptually identical to that of E2, may subserve a regulatory function in breast cancer cells.
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Willard, S.T., Frawley, L.S. TGF-α exerts biphasic effects on estrogen- and phytoestrogen-mediated gene expression in breast cancer cells. Endocr 11, 69–74 (1999). https://doi.org/10.1385/ENDO:11:1:69
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DOI: https://doi.org/10.1385/ENDO:11:1:69