Imprinted PEG3 domain at 19q13.4 and carcinogenesis

19q13.4 处的印记 PEG3 结构域与致癌作用

• 批准号: 6445446
• 负责人: Susan Kay Murphy
• 金额: $ 4.02万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-26 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6445446
• 关键词: DNA methylation; apoptosis; gene induction /repression; genetic promoter element; genetic susceptibility; genomic imprinting; molecular cloning; ovary neoplasms; p53 gene /protein; polymerase chain reaction; protein isoforms; tissue /cell culture; tumor suppressor genes; tumor suppressor proteins

DESCRIPTION (provided by applicant): This proposal is directed at determining the role of the paternally expressed gene, PEG3, in ovarian cancer, and defining other imprinted genes at human 19q13.4 potentially involved in carcinogenesis. Preliminary data indicate that PEG3 is dramatically downregulated, and that the PEG3 promoter CpG island is hypermethylated in ovarian tumors. Bisulfite sequencing of DNA from ovarian tumors will be used to determine the frequency of PEG3 promoter region hypermethylation. There are at least three alternatively spliced PEG3 isoforms that are maternally imprinted and paternally expressed in a tissue-dependent manner. Two of these isoforms encode distinct zinc finger proteins that share upstream exons independent of the zinc finger domains. The third isoform is predicted to encode a truncated protein that is expressed in tissues together with the other PEG3 isoforms with the notable exception of heart and placenta, suggesting an important tissue-specific function. Transient transfection assays using PEG3-deficient ovarian cancer cell lines will be used to determine the influence of the three isoforms on cellular growth and apoptosis, both functions previously ascribed to mouse Peg3. These studies will help clarify the role of the human PEG3 isoforms in the control of cellular growth, and may further contribute potential diagnostic and therapeutic targets for ovarian cancer.

描述（申请人提供）：该提案旨在确定 亲子表达基因PEG3在卵巢癌中的作用，以及 在人类19q13.4定义其他印迹基因可能参与 致癌作用。初步数据表明PEG3急剧 下调，PEG3启动子CpG岛在 卵巢肿瘤。来自卵巢肿瘤的DNA的Bisulfite测序将用于 确定PEG3启动子区域高甲基化的频率。有 至少三个剪接的PEG3同工型，它们是母体印刷的 并以组织依赖性方式表达。其中两个同工型 编码独立于上游外显子的不同锌指蛋白独立于上游外显子 锌指域。预计第三个同工型将编码截断 与其他PEG3同工型一起在组织中表达的蛋白质 心脏和胎盘的显着例外，表明一个重要的 组织特异性功能。使用PEG3缺陷的瞬时转染测定 卵巢癌细胞系将用于确定三个的影响 针对细胞生长和凋亡的同工型，这两个功能先前归因于 到鼠标PEG3。这些研究将有助于阐明人类PEG3的作用 在控制细胞生长中的同工型，并可能进一步贡献 卵巢癌的潜在诊断和治疗靶标。