Molecular cloning of candidate gene for human ovarian carcinogenesis

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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.