POLYPEPTIDE MODULATION IN MCF-7 CELLS BY ESTROGEN AND GROWTH FACTORS

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The purpose of this project was to utilize the established human mammary tumor cell lines (MCF-7, MCF-7(gpt) (produced by transfection with the Eco-gpt selectable gene marker), MCF- 7(ras) (produced by transfection with Eco-gpt and the v-Hras oncogene) and LY2) to investigate the effect of antiestrogens, estrogen and other growth factors on the polypeptide expression of these cells. The growth factors IGF-1 (insulin-like growth factor-1) and TGF-alpha (transforming growth factor alpha) are able to elicit many of the growth stimulating responses of estrogen when applied to the MCF-7 human mammary tumor cell line. An initial baseline study between the MCF-7, MCF-7(gpt) and MCF-7(ras) has found that there are several polypeptides expressed only in MCF-7 (14), MCF-7(gpt) (5) and MCF-7(ras) (3). A number of quantitative differences between the cell lines were apparent, with the major differences occurring between the MCF-7 - MCF-7(gpt) and MCF-7 - MCF-7(ras). Studies to assess the effect of estrogen on the cellular polypeptide expression and the effect of estrogen, IGF-1 and TGF-alpha on cellular and secreted proteins of the MCF-7, MCF-7(gpt) and MCF-7(ras) are in the final analysis stage. Additional to this are experiments using the antiestrogen LY117018 to assess the effect on polypeptide expression and secretion from the antiestrogen- resistant cell line LY2 and the MCF-7 cells.