hMLH1 and hMSH2 expression and BAX frameshift mutations in ovarian cancer cell lines and tumors

The expression of mismatch repair proteins hMSH2 and hMLH1 was investigatedin human ovarian cancer cell lines and in biopsies of ovarian carcinomasobtained from 20 patients undergoing surgical operation. By Westernblotting analysis hMSH2 protein was detected in all the tumor samplesanalyzed and in eight out of nine human ovarian cancer cell lines, whilehMLH1 was undetectable in four out of 20 ovarian tumors and in five out ofnine human ovarian cancer cell lines analyzed. The possible presence offrameshift mutations in the BAX gene, which contains a sequence of eightcontiguous guanines in its third exon, was tested in all the samples. Allthe cell lines presented the normal alleles for the BAX gene while only inone of the tumor samples a heterozygous frameshift mutation was found. Theframeshift mutation was associated to a low, almost undetectable, level ofBAX protein which was instead present at much higher levels in all theother samples investigated. The results indicate that frameshift mutationsin the BAX gene, possibly arising as a consequence of microsatelliteinstability (detectable in these tumors), is detectable in human ovariancancer although quantitatively it does not appear to be a major determinantof the low apoptotic response to chemotherapy observed in ovarian cancercells.