Analysis of p73 in human borderline and invasive ovarian tumor

p73 is a novel gene that has high sequence homology and similar gene struct ure to the tumor suppressor gene p53, We analysed p73 in seven ovarian carc inoma cell Lines and a total of 63 human borderline and invasive ovarian tu mor samples. Loss of heterozygosity at this locus was observed in 50% of in vasive tumors but in none of the borderline tumors. Biallelic expression of the gene was observed in the heterozygous tumor tissues. Direct sequencing and single-strand conformation polymorphism analyses of the p73 cDNA seque nce homologous to the highly mutatable region of p53 did not reveal any mut ations. When compared to the primary cultures of normal human ovarian surfa ce epithelial cells and immortalized cell lines, four of the seven ovarian carcinoma cell lines, 71% of the invasive tumors, and 92% of the borderline tumor tissues express elevated levels of p73 transcript. Except for the OV CA3 cell line, Western blot analysis of the nuclear extracts prepared from the cell lines showed concordant levels of p73 protein. Our analysis also d emonstrated the expression of a spliced variant of p73 transcript with the omission of exon 2 solely in the cancer cell lines and invasive tumor tissu es. This exon 2-spliced transcript would give rise to a truncated p73 prote in without the N-terminal transactivation domain. In reminiscence of the do minant negative phenotype of the N-terminal truncated variants of another p 53-related gene, p63, the expression of the truncated p73 variant form in o varian tumors may play an important role in the pathogenesis of ovarian can cer.