权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Genetic events associated with human endometrial carcinogenesis.

与人类子宫内膜癌发生相关的遗传事件。

基本信息

批准号：
03454399
负责人：
WAKE Norio
金额：
$ 3.97万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454399/
关键词：
Endometrial carcinoma genetic events K-ras gene mutation tumor suppressor genes microcell fusion LOH 遺伝子クロ-ニング

项目摘要

The present study was undertaken to disclose the involvement of multiple genetic events in neoplastic transformation of human endometrium. Microcell mediated a chromosome 1 transfer into endometrial carcinoma cells associated with the suppression of tumorigenecity and in vitro growth properties, suggesting the presence of tumor suppressor gene(s) on chromosome 1. Loss of chromosome 4 from the nontumorigenic whole cell hybrids between endometrial carcinoma cells and normal fibroblasts correlated with the recovery of tumorigenecity. In addition to these results, comprehensive analyses of allelic losses and point mutations of ras genes disclosed that at least 3 genetic events, including 18q, 17p deletions, and point mutations at codon 12 of the K-ras gene, were implicated in the development of endometrial carcinomas. Likely targets for these allelic losses were the DCC gene and the p53 gene sequences, respectively. The involvement of putative suppressor gene(s) locating on chromosome 1 in formation of hyperplastic focus with cellular atypism may be speculated by alterations of transformed phenotypes in the microcell hybrid containing an extra copy of chromosome 1. The genetic events implicating K-ras gene mutatin, loss of DCC gene and chromosome 4 deletion corresponded to the transition from hyperplasia to neoplasia. The p53 gene mutations seemed to be implicated in the progression following the development of fully malignant tumors.

本研究的目的是揭示多种遗传事件参与人类子宫内膜的肿瘤转化。微细胞介导的1号染色体转移到子宫内膜癌细胞中，与肿瘤发生和体外生长特性的抑制相关，表明1号染色体上存在肿瘤抑制基因。子宫内膜癌细胞和正常成纤维细胞之间的非致瘤性全细胞杂种的4号染色体丢失与致瘤性的恢复相关。除了这些结果，全面分析的等位基因丢失和点突变的ras基因披露，至少有3个遗传事件，包括18 q，17 p缺失，和点突变的K-ras基因的密码子12，在子宫内膜癌的发展有牵连。这些等位基因丢失的可能靶点分别是DCC基因和p53基因序列。位于1号染色体上的假定抑制基因参与了具有细胞增殖的增生灶的形成，可以通过含有额外1号染色体拷贝的微细胞杂种中转化表型的改变来推测。K-ras基因突变、DCC基因缺失和4号染色体缺失的遗传事件与乳腺增生向肿瘤转变相一致。p53基因突变似乎与完全恶性肿瘤发展后的进展有关。