The inactivation of the tumor suppressor gene p53 has been demonstrated in a variety of human
tumors. Herein, we performed a p53 gene analysis of human gynecologic tumor cell lines and
tumor tissues. In the SK-OV-3 cell line, Southern analysis suggested the presence of sequence deletions/rearrangements in at least one allele of p53 gene. Transcripts were not detectable by either Northern or PCR analysis. Sequencing analysis of the entire coding region revealed mutations changing the p53
amino acid composition in all six
endometrial carcinoma cell lines tested (Ishikawa, Hec1-A, Hec1-B, KLE, RL95-2, and
AN-3), and four cell lines in ovarian
carcinoma cell lines (Caov-3, -4, OVCAR-3, and Kuramochi). Of the seven cervical
carcinoma cell lines, two (HT-3 and C-33A) contained p53
codon changes. We were unable to detect the human papilloma virus (HPV) in these two cell lines. By contrast, five HPV-positive cervical
carcinoma cell lines (HeLa S-3, Caski, SiHa, C-41, and ME-180) contained wild-type p53 gene sequences. Examination of loss of heterozygosity (LOH) by PCR revealed that about 30% of the human ovarian
carcinoma tissues has LOH at the locus of p53 gene. We suggest that, in the HPV-positive cervical
tumors, p53 inactivation occurred via the known mechanism of viral E6/cellular p53
protein association, whereas in all other
tumors (ovarian
carcinoma, endometrial carcinoma, HPV-negative cervical
carcinoma) p53 function was compromised by changes in the amino acid sequence.