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Molecular cloning of candidate gene for human ovarian carcinogenesis

人卵巢癌候选基因的分子克隆

基本信息

批准号：
09671657
负责人：
ISHIKAWA Mutsuo
金额：
$ 1.98万
依托单位：
ASAHIKAWA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671657/
关键词：
uterine ovary cancer p15 p16 PTEN 発癌 IGF-II P15 P16 Rb

项目摘要

The mRNA for p14ARF is composed of exons 1b, 2, and 3, whereas the mRNA for p16ィイD2INK4AィエD2 is derived from exons 1a, 2, and 3 . Alternative splicing of exon 1 in p14ィイD2ARFィエD2 results in a different reading frame for exons 2 and 3. Pl4ィイD2ARFィエD2 inhibits the expression of oncogene MDM-2, therefore preventing MDM-2-mediated inactivation of tumor suppressor gene p53. In an effort to analyze molecular mechanisms of human gynecologic carcinogenesis, we studied the structure and expression of the p14ィイD2ARFィエD2 gene. For ovarian cancer cell lines, only small amount of p14ィイD2ARFィエD2 gene expression was observed in PA-1 cell line, and no p14ARF gene was expressed in SK-OV-3 cell line. P14ィイD2ARFィエD2 1b genomic DNA was lost in SK-OV-3 cell line. Loss of p14ィイD2ARFィエD2 gene expression was seen in 10 % (5/46) of ovarian cancer tissues, and p14ィイD2ARFィエD2 1b genomic DNA was lost in 9% (4/46) of ovarian cancer tissues. Low expression was seen in 9% (4/46) of ovarian cancer tissues compared to normal counterparts. On the other hands, for uterine cancers, in all thirteen cell lines and 80 uterine cancer tissues, p14ィイD2ARFィエD2 gene abnormality was not detected using RT-PCR and SSCP analysis. These data suggest that abnormalities of p14ィイD2ARFィエD2 gene may be involved in some human ovarian carcinogenesis, but not in uterine carcinogenesis.

p14 ARF的mRNA由外显子1b、2和3组成，而p16 ARF D2 INK 4A ARF D2的mRNA来自外显子1a、2和3。p14外显子D2 ARF外显子D2中外显子1的选择性剪接导致外显子2和3的不同阅读框架。P14 β D2 ARF β D2抑制癌基因MDM-2的表达，因此阻止MDM-2介导的肿瘤抑制基因p53的失活。为了分析人类妇科肿瘤发生的分子机制，我们研究了p14 β D2 ARF β D2基因的结构和表达。在卵巢癌细胞系中，PA-1细胞系中仅观察到少量p14 ARF基因的表达，而SK-OV-3细胞系中未观察到p14 ARF基因的表达。SK-OV-3细胞系中P14 β D2 ARF β D2 1b基因组DNA丢失。10%（5/46）的卵巢癌组织中p14外显子D2 ARF外显子D2基因表达缺失，9%（4/46）的卵巢癌组织中p14外显子D2 ARF外显子D2 1b基因组DNA表达缺失。9%（4/46）的卵巢癌组织中低表达。另一方面，对于子宫癌，在所有13个细胞系和80个子宫癌组织中，使用RT-PCR和SSCP分析未检测到p14 β D2 ARF β D2基因异常。这些结果提示，p14 β D2 ARF β D2基因异常可能参与了某些人卵巢癌的发生，但与子宫癌的发生无关。