HMGA2：一个潜在预测乳腺癌患者阿霉素治疗疗效的标记物及其分子机理的研究

项目名称： HMGA2：一个潜在预测乳腺癌患者阿霉素治疗疗效的标记物及其分子机理的研究

项目编号： No.81202098

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 王晓晨

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 30年以来，以阿霉素为基础的化疗方案一直是乳癌化疗的基石。但阿霉素有很多的副作用：骨髓抑制、肝损及心衰等。因此有必要寻找特异的标记物来鉴定适合化疗的人群以提高疗效降低副反应。HMGA2高表达与乳癌不良预后密切相关。我们发现HMGA2高表达可提高乳癌细胞对阿霉素的敏感性，提示HMGA2有可能作为一个判断阿霉素疗效的指标。HMGA2在乳腺肿瘤发展过程中的作用机制目前尚不清楚。我们发现高表达的HMGA2通过调节细胞对DNA损伤的反应，来提高乳癌细胞HS578T对阿霉素的敏感性。本研究中心假设：阿霉素通过依赖HMGA2的途径来提高细胞毒性；HMGA2促进DNA损伤积聚和肿瘤发展。我们将分析乳癌患者对阿霉素的敏感性和HMGA2表达之间的关系。随后在分子水平上的分析将有助于理解HMGA2介导阿霉素增敏的机制。可预见的是：HMGA2能用于判断阿霉素治疗的敏感性，有助于制定优化的化疗策略，寻找新的靶分

中文关键词： HMGA2；乳腺癌；病理分级；三阴性乳腺癌；预后

英文摘要： Breast cancer is one of the most common cancer diagnosed in women in China. Once diagnosed, it is treated by a combination of modalities including surgery, chemotherapy, radiation and hormonal therapy. Treatment is influenced by age, menopausal status, pathology (eg. nuclear and histological grades), estrogen and progesterone receptor status and Her2/neu gene amplification. For over 30 years, doxorubicin (Dox) has been the mainstay in the treatment of breast cancer. Its clinical benefits are often plagued by severe side effects including myelosuppression, hepatic toxicity and congestive heart failure, which may require dose reduction or even discontinuation of the drug. Hence, there is a need to identify patient populations or other synergistic factors to improve treatment outcome and to minimize undesired side effects. In order to improve clinical outcomes with Dox-treatment, we have identified the high-mobility group A2 (HMGA2) expression as a therapeutic marker. HMGA2 has been known to be an indicator for poor prognosis and has also been associated with tumor metastasis in breast cancer. We have found that HMGA2 expression sensitizes breast cancer cells to Dox-treatment and may provide a novel role as a therapeutic marker for rendering Dox chemosensitivity in breast cancer treatment. The underlying m

英文关键词： HMGA2；breast cancer；histopathological grade；triple-negative breast cancer；prognosis