MOLECULAR MECHANISMS OF ESTROGEN INDUCED CELL GROWTH

这项拟议的研究将调查乳腺癌细胞中雌激素增殖作用所涉及的分子事件。 我们将探讨MAPK信号转导级联反应作为一个潜在的途径利用雌激素引起乳腺细胞增生。 这可能会导致识别乳腺组织中雌激素作用的分子靶点，从而产生用于治疗或预防乳腺癌的新药物疗法。 雌激素诱导MAPK途径的生理和/或形态学效应尚未在任何细胞类型中研究，因此为研究雌激素诱导乳腺/乳腺癌细胞增生的方法提供了逻辑起点。这些研究将通过使用标准增殖试验（MTS和3 H掺入）来测量人乳腺癌细胞（MCF-7）对雌激素治疗的反应来完成。 还将进行MAPK或MAPK相关酶活性的直接测量。 将突变的MAPK酶转染到MCF-7细胞中，以确定它们的活性是否是雌激素增殖效应所必需的。然后将评价通过MAPK级联启动而转变的基因，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.