Molecular Studies of Ovarian Cancer and the Wnt Pathway in Human Cancer

卵巢癌和人类癌症 Wnt 通路的分子研究

• 批准号: 6431426
• 负责人: Patrice J. Morin
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431426
• 关键词: carcinogenesis; gene expression; genetic techniques; human genetic material tag; human tissue; molecular genetics; molecular oncology; neoplasm /cancer genetics; ovary neoplasms; tumor suppressor genes

These studies focus on two topics: ovarian cancer and the Wnt pathway in human cancers. Ovarian cancer is the fifth most common cancer and the fourth leading cause of cancer death among women in the United States. Because of a lack of powerful screening and diagnostic tests, early detection has been difficult. Moreover, the molecular mechanisms involved in the initiation and progression of ovarian cancer remain largely unknown. We are using SAGE and other state-of-the-art molecular techniques to identify tumor markers and gain a greater understanding of the molecular pathways involved in ovarian tumorigenesis. In addition, we are interested in a region on the chromosome 6, which appears to be lost early in ovarian cancer, suggesting the presence of a tumor suppressor gene involved in the first stages of tumor development. We have now found a homozygous deletion spanning approximately 85 kb at 6q26 in an ovarian cancer cell line. This homozygous deletion may help us to identify the 6q tumor suppressor gene. The Wnt pathway, which was originally defined as a crucial pathway for body patterning during fruit fly development, has recently been implicated in human cancer. APC, a gene mutated in 80% of all colon cancers, is involved in the downregulation of the Wnt pathway. Moreover, colon tumors containing wild-type APC, frequently contain activating mutations in other members of the pathway emphasizing its importance for colon cancer progression. We are developing inducible systems that may be useful in the identification of downstream transcriptional targets as well as upstream regulatory components of the pathway .

这些研究侧重于两个主题：卵巢癌和人类癌症中的WNT途径。 卵巢癌是美国女性第五大癌症，也是癌症死亡的第四个主要原因。由于缺乏强大的筛查和诊断测试，很难早期检测。 此外，卵巢癌的起始和进展涉及的分子机制在很大程度上尚不清楚。 我们正在使用SAGE和其他最先进的分子技术来鉴定肿瘤标记，并对参与卵巢肿瘤发生的分子途径有更深入的了解。此外，我们对6号染色体上的一个区域感兴趣，该区域似乎在卵巢癌中丧失了，这表明存在肿瘤抑制基因参与肿瘤发育的第一阶段。 现在，我们发现在卵巢癌细胞系中，纯合缺失在6q26时占85 kb。 这种纯合缺失可能有助于我们鉴定6Q肿瘤抑制基因。 Wnt途径最初被定义为在果蝇发育过程中的身体模式的关键途径，最近与人类癌症有关。 APC是所有结肠癌中80％突变的基因，参与WNT途径的下调。 此外，含有野生型APC的结肠肿瘤经常包含该途径其他成员的激活突变，这强调了其对结肠癌进展的重要性。我们正在开发可诱导系统，这些系统可能可用于识别下游转录靶标以及该途径的上游调节组件。