MOLECULAR MECHANISMS OF ESTROGEN INDUCED CELL GROWTH

这项拟议的研究将调查雌激素在乳腺癌细胞中的增殖作用所涉及的分子事件。我们将研究MAPK信号转导通路作为雌激素引起乳腺细胞增殖的潜在途径。这可能会导致确定乳腺组织中雌激素作用的分子靶点，以针对这些靶点产生治疗或预防乳腺癌的新药物疗法。雌激素诱导MAPK通路的生理和/或形态效应尚未在任何细胞类型中被研究，因此为研究雌激素诱导乳腺/乳腺癌细胞增殖的途径提供了一个逻辑起点。这些研究将通过使用标准的增殖分析(MTS和~3H掺入)来测量人类乳腺癌细胞(MCF-7)对雌激素治疗的反应来完成。还将进行MAPK或与MAPK相关的酶活性的直接测量。突变的MAPK酶将被导入MCF-7细胞，以确定它们的活性是否对雌激素的增殖作用是必要的。然后将评估通过启动MAPK级联而启动的基因，如细胞周期蛋白D1。

The proposed research will investigate the molecular events involved in the proliferative actions of estrogen in breast cancer cells. We will investigate the MAPK signal transduction cascade as a potential pathway utilized by estrogen to cause the hyperplasia of breast cells. This could potentially lead to the identification of molecular targets for the actions of estrogen in breast tissue against which to generate new pharmacotherapies for the treatment or prevention of breast cancer. The physiologic and/or morphologic effects of the estrogen induction of the MAPK pathway has not yet been investigated in any cell type and therefore presents a logical starting point for the investigation of the means by which estrogen induces the proliferation of hyperplasia of breast/breast cancer cells. These studies will be accomplished by utilizing standard proliferative assays (MTS and 3H incorporation) to measure the growth of human breast cancer cells (MCF-7) in response to estrogen treatment. Direct measurements of MAPK or MAPK related enzymatic activities will also be performed. Mutant MAPK enzymes will be transfected into MCF-7 cells to determine if their activity is necessary for the proliferative effects of estrogen. The genes that are turned by initiation of the MAPK cascade such as cyclin D1 will then be evaluated.