Estrogen-stimulated mammary tumor growth has been demonstrated both in vivo and in vitro. However, the mechanism of estrogen-induced cell proliferation has not been elucidated. This proposal is an extension of previous studies aimed at elucidating this mechanism. A breast cancer cell line, CAMA -1, is used as an in vitro model for this study. Synchronized cell populations at the early G1, late G1 and G2/M phases will be used to evaluate the effects of estrogen and anti-estrogens on the synthesis of growth factors (GFs) and growth inhibitors (GIs), the effects of GFs and GIs on tumor growth with and without estrogen, and the effects of estrogen and anti-estrogens on receptors of these GFs and GIs. Antibodies (monoclonal or polyclonal) to these GFs and GIs are used for establishing immono methods for qualitative and quantitative analysis of the GFs and GIs and their cognate membrane receptors. The effects to these antibodies on cell proliferation will also be evaluated. Cell proliferation will be determined by flow cytometry, 3H-thymidine uptake and autoradiography. Estrogen-increase G1 phase transverse to S phase has been shown previously for CAMA-1. The proposed experiments are aimed at elucidating estrogen- regulated events at the G1 phase that are related to estrogen- induced G1 phase exit, and testing the hypothesis that estrogen- induced cell proliferation is mediated by GFs. Results from this study will provide pertinent information of fundamental, clinical and therapeutical importance.
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