Analysis of genetic abnormalities in gynecologic malignancies, especially endometrial cancer and ovarian cancer

在本研究中，我们报道了子宫内膜癌中复制错误（RER）的频率明显高于卵巢癌，并且在单个子宫内膜癌中检测到两个hMLH1体细胞突变，RER在子宫内膜癌的癌变和进展中起重要作用，RER（+）肿瘤患者的生存率较差。关于卵巢癌，我们报道了肿瘤抑制基因产物的蛋白相互作用。如p53或Rb与73 kDa热休克同源蛋白在卵巢癌细胞系。在肿瘤免疫学中，细胞表面抗原在卵巢癌细胞的癌变过程中与HSP相关，HSP在器官移植中的排斥反应和作为ctl靶向肿瘤排斥抗原的重要性被报道。在人类卵巢癌中，我们分析了hsc73与p53或Rb基因产物之间的关系。p53是一个独立的预后因素，即使在p53阴性的病例中，hsc73过表达和pRB表达降低也是重要的预后因素。此外，我们在卵巢癌中检测到染色体6q27上含有假定的肿瘤抑制基因的300 kb片段的一个常见缺失区域。通过对人卵巢肿瘤端粒酶活性的分析，其活性水平在良性、LMP和恶性肿瘤中均有所升高，但与临床预后因素无关。通过对细胞周期调节蛋白的分析，我们发现细胞周期调节蛋白的退化上调了人卵巢癌的端粒酶活性。这是人类肿瘤中端粒酶活性与细胞周期调节蛋白相互作用的首次报道。关于卵巢癌细胞的化疗敏感性，我们分析了紫杉醇或CDDP化疗期间细胞凋亡的关系。从这些药物诱导的细胞凋亡过程中DNA片段的定量来看，细胞凋亡需要超过恒定水平的药物刺激，不同细胞系的DNA片段不同。从IL-6给药实验来看，高剂量IL-6可阻止cddp诱导的细胞凋亡。少

In the current study, we reported that the frequency of replication error (RER) in endometrial cancer was significantly higher than that of ovarian cancer and two somatic mutations of hMLH1 were detected in a single endometrial cancer and RER was important in the carcinogenesis and progression of endometrial cancer, with poorer survival of the patients with RER(+) tumor.Concerning to ovarian cancer, we reported the protein interaction of tumor suppressor gene products. such as p53 or Rb with 73 kDa heat shock cognate protein in ovarian cancer cell lines. In tumor immunology, cellular surface antigens were associated with HSP in the carcinogenesis of ovarian cancer cells and the importance of HSP was reported at the rejection in the organ transplantation and as CTL-targeted tumor rejection antigens. In human ovarian cancer, we performed an analysis of the association between hsc73 and p53 or Rb gene products. p53 was an independent prognostic factor, and even in the p53 negative cases, … More hsc73 overexpression and reduced pRB expression were also important as the prognostic factor. Furthermore, we detected a commonly deleted region in ovarian cancers to a 300-kb segment of chromosome 6q27 containing the putative tumor suppressor gene.Under the analysis of telomerase activity in human ovarian tumor, the level of its activities was increased from benign, LMP,and malignant tumors, but not associated with clinical prognostic factors. From the analysis with cell cycle-regulated protein, we found that degeneration of cell cycle regulatory proteins upregulated telomerase activity in human ovarian cancer.This is a first report of the interaction between telomerase activity and cell cycle-regulated protein in human tumor.About the chemosensitivity of ovarian cancer cells, we analyzed the association of apoptosis during Taxol or CDDP containing chemotherapy. From the quantitation of DNA fragmentation during these drug-induced apoptosis, apoptosis was required with more than constant level of drug stimuli and DNA fragmentation varied in the different cell lines. From the experiments of IL-6 administration, CDDP-induced apoptosis was prevented with high doses of IL-6. Less