Role of BRCA1 in controlling mitotic arrest in ovarian cystadenoma cells.

摘要: Cancers that develop in BRCA1 mutation carriers are usually near tetraploid/polyploid. This led us to hypothesize controls the mitotic checkpoint complex, as loss of such control could lead errors resulting tetraploidy/polyploidy with subsequent aneuploidy. We used an vitro system mimicking pre-malignant conditions, consisting cell strains derived from benign counterparts serous ovarian carcinomas (cystadenomas) and expressing SV40 large T antigen, conferring equivalent a p53 mutation. previously showed cells undergo one or several doublings their DNA content they age culture approach phenomenon crisis. Here we show increase reflects cycle arrest possibly at anaphase promoting evidenced by decreased BrdU incorporation increased expression complex. Down-regulation undergoing crisis leads activation complex resumption growth kinetics similar those seen before reach Cells recovering after down-regulation become multinucleated, suggesting reduced may initiation new without completion cytokinesis. is first demonstration physiological M phase apart its established role damage response, represent important mechanism for acquisition aneuploidy during tumor development. be particularly relevant cancers have tetraploid/polyploid number chromosomes.