Expression profiles of BRCA1 splice variants in asynchronous and in G1/S synchronized tumor cell lines

Disrupting the function of the BRCA1 gene by mechanisms other than germline mutations is suspected to occur in cases of sporadic breast/ovarian cancer s. Using ribonuclease protection assay and multiplex RT-PCR, we examined th e change of the total BRCA1 mRNA pool and the expression profile of four pr edominant BRCA1 splice variants in asynchronous and in G1/S synchronized tu mor cell populations compared to normal breast cells. Experiments were carr ied 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), th e Delta (9,10), and the Delta (9,10,11q) BRCA1 isoforms showed different ex pression patterns in the examined breast and ovarian tumor cell lines as co mpared to the leukemia cell line. This observation raises the possibility t hat the dysregulation of alternative splicing of the BRCA1 gene could be in volved in tumor formation in the breast and the ovary, even in the absence of germline mutations. (C) 2001 Academic Press.