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MOLECULAR GENETICS OF HUMAN GYNECOLOGIC PATHOLOGY

MOLECULAR GENETICS OF HUMAN GYNECOLOGIC PATHOLOGY
人类妇科病理学的分子遗传学
批准号:
6162149
负责人:
JAMES C. BARRETT
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
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中文摘要
翻译
肿瘤分子遗传学研究综述 女性生殖器官包括子宫内膜的状况 癌、子宫肉瘤、乳腺癌、子宫肌瘤和 卵巢癌正在研究中。对这些癌症的分析, 尤其是子宫内膜癌已经定义了一个子集,它具有 微卫星不稳定性的分子遗传表型。 遗传性非息肉病患者的微卫星不稳定性 结直肠癌,是基因遗传改变的结果 参与DNA错配修复。突变分析未能找到 散发性子宫内膜和卵巢中HNPCC基因的改变 具有微卫星不稳定性的癌症。几个候选基因 (基于与其他错配修复基因的序列相似性) 分析了这些样本中的变化。其中,hMSH3被发现 在几个子宫内膜肿瘤和细胞系中发生改变。介绍 HMSH3在hMSH3突变细胞系中的正常复制恢复了某些 有缺陷的DNA修复和极大地减少了 微卫星在该细胞系中的不稳定性。还介绍了hMSH6 恢复的DNA修复表型表明hMSH3和hMSH6共有 部分冗余的功能。我们还发现了有缺陷的细胞系 在hPMS2错配修复基因中表达,并通过cDNA对其功能进行补充 转染法。HMSH3/hMSH6和hPMS2恢复的细胞正在 用于确定细胞之间是否存在相互作用 循环机械和错配修复。DNA修复过程需要 细胞停滞在细胞周期的某些阶段,称为检查点。 目前的研究集中在了解错配修复是如何进行的 系统与细胞周期机制协调,以停止细胞周期 进展,并允许在暴露于破坏性物质后进行修复。也是 正在研究的是位于第1、10和14号染色体上的等位基因缺失区域 子宫内膜癌。这些区域的精细测绘可能会导致 子宫内膜癌发生相关基因的鉴定。
英文摘要
Summary of Work: The molecular genetics analysis of neoplastic conditions of the female reproductive organs including endometrial carcinoma, uterine sarcoma, breast carcinoma, uterine leiomyoma, and ovarian carcinoma are under study. Analysis of these cancers, particularly endometrial cancer has defined a subset that have the molecular genetic phenotype of microsatellite instability. Microsatellite instability in individuals with hereditary non polyposis colorectal carcinoma, is the result of inherited alterations in genes involved in DNA mismatch repair. Mutational analysis fails to find alterations of the HNPCC genes in many sporadic endometrial and ovarian carcinomas with microsatellite instability. Several candidate genes (based on sequence similarity to other mismatch repair genes) were analyzed for alterations in these samples. Of these, hMSH3, was found to be altered in several endometrial tumors and cell lines. Introduction of a normal copy of hMSH3 into a hMSH3 mutant cell line restored certain aspects of defective DNA repair and drastically reduced the microsatellite instability in this cell line.Introduction of hMSH6 also restored DNA repair phenotypes indicating that hMSH3 and hMSH6 share partly redundant functions. We have also identified cell lines defective in the hPMS2 mismatch repair gene and complemented its function by cDNA transfection. The hMSH3/hMSH6 and hPMS2 restored cells are being utilized to determine whether there is an interaction between the cell cycle machinery and mismatch repair. The DNA repair process requires cellular arrest at certain stages of the cell cycle known as checkpoints. Current research is focused on understanding how the mismatch repair system coordinates with the cell cycle machinery to stop cell cycle progression and allow repair following exposure to damaging agents. Also under study are regions of allele loss on chromosomes 1, 10 and 14 in endometrial carcinomas. Fine mapping of these regions may lead to the identification of genes involved in endometrial carcinogenesis.
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A METASTASIS SUPPRESSOR GENE FOR PROSTATIC CANCER
APOPTOSIS AND AIDS--ROLE OF TAT GENE
Cell Senescence, Carcinogenesis, and Aging
  • 批准号:
    6559271
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    JAMES C. BARRETT
  • 依托单位:
SIGNALING OF APOPTOSIS DURING CELL TRANSFORMATION
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