Disrupting the function of the BRCA1 gene by mechanisms other than germline mutations is suspected to occur in cases of sporadic breast/ovarian cancers. Using ribonuclease protection assay and multiplex RT-PCR, we examined the change of the total BRCA1 mRNA pool and the expression profile of four predominant BRCA1 splice variants in asynchronous and in G1/S synchronized tumor cell populations compared to normal breast cells. Experiments were carried out on MCF-7 and MDA-MB-231 breast cancer, OVCAR-5 ovarian cancer, and K562 leukemia cell lines. The ratio of the full length, the delta(11q), the delta(9,10), and the delta(9,10,11q) BRCA1 isoforms showed different expression patterns in the examined breast and ovarian tumor cell lines as compared to the leukemia cell line. This observation raises the possibility that the dysregulation of alternative splicing of the BRCA1 gene could be involved in tumor formation in the breast and the ovary, even in the absence of germline mutations.
Copyright 2001 Academic Press.