Resveratrol in breast cancer cell survival or apoptosis

白藜芦醇对乳腺癌细胞存活或凋亡的影响

• 批准号: 7037577
• 负责人: SURANGANIE DHARMAWARDHANE
• 金额: $ 7.23万
• 依托单位: UNIVERSIDAD CENTRAL DEL CARIBE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7037577
• 关键词: Resveratrol; breast; cancer; cell; survival

DESCRIPTION (provided by applicant): Signaling via estrogen receptors (ER) and epidermal growth factor receptors (EGFR) are critical for normal mammary gland development as well as breast cancer initiation and progression. Recent studies on rapid effects of estrogen, including our preliminary and published data, indicate that estrogen signaling is complex and may involve non-genomic pathways that facilitate cross-talk with EGFR signaling. The estrogen-like steroidal compound of red wine and grape skins, resveratrol, has been linked to cancer prevention. In ER alpha (+) breast cancer cells, resveratrol has been shown to promote growth arrest and apoptosis. Our published and preliminary data demonstrate ER isoform status-dependent resveratrol effects on breast cancer cell survival by modulation of the activity of the protooncogene Akt. The objective of this application is to elucidate the role of ER and EGFR isoforms on resveratrol-mediated breast cancer cell proliferation or arrest. The central hypothesis of this application is that signaling for breast cancer cell cycle progression or arrest by resveratrol is dependent on ER isoform status. The rationale for the proposed research is that elucidation of the role of resveratrol as a modulator of cell death or survival and proliferation is important for ascertaining a dual role for resveratrol as a breast cancer preventive and a promoter of established breast cancer. Our experimental approach for testing this hypothesis is to analyze relative cell cycle progression in a ER negative breast cancer cell line that ectopically express vector alone, ER alpha, ER beta, or both ER isoforms. Our first specific aim is to determine the activation status of ER alpha, beta, or EGFR following resveratrol treatment in the presence or absence of ER or EGFR specific inhibitors. Our second specific aim is to investigate the effect of modulating ER or EGFR activity on resveratrol-mediated cell cycle progression in the same range of cell lines. This will be achieved by analysis of the effect of resveratrol on cell cycle progression in the presence or absence of inhibitors to ER or EGFR. This timely research promises to fill the considerable gap in our current knowledge concerning the efficacy of resveratrol as a preventive for both women at high risk and survivors of breast cancer.

描述（由申请人提供）：通过雌激素受体（ER）和表皮生长因子受体（EGFR）发出的信号对于正常乳腺发育以及乳腺癌的发生和进展至关重要。最近关于雌激素快速作用的研究，包括我们的初步和已发表的数据，表明雌激素信号传导很复杂，并且可能涉及促进与 EGFR 信号传导串扰的非基因组途径。红酒和葡萄皮中的类雌激素类固醇化合物白藜芦醇与预防癌症有关。在 ER α (+) 乳腺癌细胞中，白藜芦醇已被证明可以促进生长停滞和细胞凋亡。我们发表的初步数据表明，ER 亚型状态依赖性白藜芦醇通过调节原癌基因 Akt 的活性对乳腺癌细胞存活产生影响。本申请的目的是阐明 ER 和 EGFR 同工型对白藜芦醇介导的乳腺癌细胞增殖或停滞的作用。本申请的中心假设是白藜芦醇对乳腺癌细胞周期进展或停滞的信号传导依赖于 ER 同工型状态。拟议研究的基本原理是，阐明白藜芦醇作为细胞死亡或存活和增殖调节剂的作用对于确定白藜芦醇作为乳腺癌预防剂和已形成乳腺癌促进剂的双重作用非常重要。我们检验这一假设的实验方法是分析 ER 阴性乳腺癌细胞系中的相对细胞周期进展，这些细胞系异位表达单独的载体、ER α、ER β 或两种 ER 亚型。我们的第一个具体目标是确定在存在或不存在 ER 或 EGFR 特异性抑制剂的情况下，白藜芦醇治疗后 ER α、β 或 EGFR 的激活状态。我们的第二个具体目标是研究在相同范围的细胞系中调节 ER 或 EGFR 活性对白藜芦醇介导的细胞周期进展的影响。这将通过分析白藜芦醇在存在或不存在 ER 或 EGFR 抑制剂的情况下对细胞周期进展的影响来实现。这项及时的研究有望填补我们目前关于白藜芦醇预防乳腺癌高危女性和幸存者功效的知识空白。