ESTROGEN-MEDIATED CELL CYCLE ARREST VIA P53 AND P21

通过 P53 和 P21 雌激素介导的细胞周期停滞

• 批准号: 7715991
• 负责人: Jay W Wright
• 金额: $ 2.77万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715991
• 关键词: Biological Assay; Biology; CDKN1A gene; Cell Cycle Arrest; Cells; Computer Retrieval of Information on Scientific Projects Database; Data; Dominant-Negative Mutation; Environment; Epithelium; Estrogen Receptor alpha; Estrogen Receptors; Estrogens; Failure; Funding; Grant; Hormones; Human; In Vitro; Incidence; Institution; Macaca mulatta; Malignant Neoplasms; Malignant neoplasm of ovary; Mediating; Menstrual cycle; Nature; Numbers; Ovarian; Ovulation; Proteins; Rate; Reproduction; Research; Research Personnel; Resources; Risk; Role; Source; Steroids; Surface; System; TP53 gene; Therapeutic; United States National Institutes of Health; Woman; base; cancer cell; experience; nonhuman primate; novel; oncoprotein p21; research study; success

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The ovarian surface epithelium (OSE) is the primary source of ovarian cancers in women, yet little is known about its normal biology or the basis of its high rate of transformation. Because the incidence of ovarian cancer correlates highly with the number of ovulations a woman experiences, it is possible that ovarian function itself places the OSE at risk for transformation. We developed a culture system to study the effects of ovarian factors - most notably steroid and protein hormones associated with reproduction - on human and nonhuman primate OSE cells grown in vitro. During the natural menstrual cycle, estrogen levels peak at micromolar concentrations in the local ovarian environment. We demonstrated that these concentrations induce cell cycle arrest in human ovarian cancer cells and normal human and rhesus OSE cells. Current data suggest this arrest is mediated by functional interactions between the estrogen receptor alpha (ER), p53 and p21, but the nature of these interactions is unknown. We therefore proposed a set of experiments to define the roles of these proteins in mediating estrogen-dependent cycle arrest, by assaying p53 activation, inhibiting p53 function, and transfecting normal or deficient cells with wild type ER, p53, and/or dominant negative p53. This novel function of the estrogen receptor may be important in understanding the mechanisms of hormone-based cancer therapeutic success and failure.

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