ESTROGEN REGULATION OF BREAST CANCER CELL PROLIFERATION

描述：这项研究的长期目标是了解 雌激素和抗雌激素调节人乳腺癌细胞的增殖， 最初需要雌激素的细胞最终是如何增殖的 变得不依赖雌激素，并对抗雌激素产生抗药性。实现这些目标 目标是至关重要的，因为雌激素独立性和 抗雌激素耐药是乳房治疗失败的主要原因 癌症患者。将采取的方法是将监管与 细胞内细胞周期蛋白/CDK信号转导通路控制细胞增殖 雌激素非依赖性乳腺癌细胞株MCF-7的研究 和MCF-7的抗雌激素抗性衍生物，以及在一组其他ER+ 和ER--乳腺癌细胞株。此外，还将进行实验 以确定干扰细胞周期蛋白/CDK途径是否可以直接 将MCF-7细胞转化为雌激素非依赖性和/或雌激素抵抗。在……里面 目的一、比较蛋白质水平和CDK活性的调节 上述细胞系。在AIMS II-IV中，细胞周期蛋白/CDK途径将 以多种方式被干扰，包括抑制细胞周期蛋白/CDK Rb功能的活性、抑制和细胞周期蛋白基因的过度表达 这些扰动对FMCF-7细胞激素依赖性的影响 将会被检查。这些研究将确定雌激素的重要靶点。 和抗雌激素作用，并提出了乳房 肿瘤可以变得不依赖雌激素，并对抗雌激素产生耐药性。

DESCRIPTION: The long term goals of this research are to understand how estrogen and antiestrogens regulate human breast cancer cell proliferation, an how cells that initially require estrogen to proliferate eventually become estrogen independent and antiestrogen resistant. Attaining these goals is critical, since the development of estrogen independence and antiestrogen resistance is a major cause of treatment failure in breast cancer patients. On approach that will be taken is to compare regulation of the intracellular cyclin/CDK pathway that controls cell proliferation in the estrogen dependent breast cancer cell line MCF-7, in estrogen independent and antiestrogen resistant derivatives of MCF-7, and in a panel of other ER+ and ER- breast cancer cell lines. In addition, experiments will be carried out to determine whether perturbing the cyclin/CDK pathway can directly convert MCF-7 cells to estrogen independence and/or estrogen resistance. In Aim I, the regulation of protein levels and CDK activity will be compared in the cell lines described above. In Aims II-IV, the cyclin/CDK pathway will be disrupted in a variety of ways including inhibition of cyclin/CDK activity, inhibition of RB function, and overexpression of cyclin genes, and the effects of these perturbations on hormone dependence of fMCF-7 cells will be examined. These studies will identify important targets of estrogen and antiestrogen action, and suggest possible mechanisms by which breast tumors can become estrogen independent and antiestrogen resistant.