BREAST CANCER CELL PROLIFERATION BY GROWTH FACTORS

生长因子引起的乳腺癌细胞增殖

• 批准号: 2390839
• 负责人: Kaladhar B. Reddy
• 金额: $ 10.15万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-14 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2390839
• 关键词: MCF7 cell; binding proteins; biological signal transduction; breast neoplasms; cell cycle; cell growth regulation; chemical association; enzyme activity; enzyme substrate; epidermal growth factor; estradiol; estrogen receptors; growth factor; growth factor receptors; mammary epithelium; neoplastic cell; phosphatidylinositols; phospholipase C; phosphorylation; protein tyrosine kinase; receptor binding; receptor expression; tamoxifen; transforming growth factors; western blottings

DESCRIPTION (Adapted from the applicant's abstract): This proposal describes biochemical studies designed to delineate specific intracellular signaling pathways involved in the regulation of cell proliferation via TGF-a /EGF-receptor binding interactions. These pathways include TGF-a-induced EGF-R phosphorylation, the association of receptor binding proteins including phospholipase C (PLC-gamma), 3'- phosphotidyl inositol protein kinase (PI 3K ) and src-family tyrosine kinase with non-catalytic regions of EGF-R. Additionally the applicant proposes that c-Ha-ras activation may be required for the mitogenic response of breast cancer cells to TGF-a or EGF and this will be evaluated. The objectives of this proposal are 1) to define differences in ligand-dependent cell proliferation induced by EGF-R phosphorylation in normal and malignant breast cells, 2) to inactivate EGF-R by introducing mutations in the tyrosine kinase binding domain and to study biochemical events occurring before and after binding of TGF-a or EGF to normal and mutant EGF-R expressing cells and 3) to elucidate the role of c-Ha-ras activation and signaling molecules such as ras GAP (GTP ase- activating protein) in TGF-a/EGF-mediated signal transduction in normal and mutant ras transfected cells. The long range goal of the proposed studies is to identify molecular events underlying tumor progression which may be potential targets for the development of rational therapeutic agents.

描述（改编自申请人摘要）：本提案 描述了生物化学研究，旨在描绘特定的 细胞内信号通路参与调节细胞 通过TGF-α/EGF-受体结合相互作用增殖。 这些 途径包括TGF-α诱导的EGF-R磷酸化， 受体结合蛋白，包括磷脂酶C（PLC-γ），3 '- 磷脂酰肌醇蛋白激酶（PI 3 K）和src家族酪氨酸 具有EGF-R的非催化区域的激酶。此外，申请人 提出c-Ha-ras的激活可能是促有丝分裂的 乳腺癌细胞对TGF-α或EGF的反应，这将是 评估。 本提案的目标是：（1）确定差异 EGF-R磷酸化诱导的配体依赖性细胞增殖 在正常和恶性乳腺细胞中，2）通过 在酪氨酸激酶结合结构域中引入突变，并研究 在TGF-α或EGF结合到细胞表面之前和之后发生的生物化学事件。 正常和突变型EGF-R表达细胞和3）阐明 c-Ha-ras激活和信号分子如ras GAP（GTP酶- TGF-α/EGF介导的信号转导中的作用 和突变ras转染的细胞。 拟议的长期目标 研究的目的是确定肿瘤进展背后的分子事件 这可能是开发合理的 治疗剂。