Mechanism of cytokinesis failure in ovarian cystadenomas with defective BRCA1 and P53 pathways.

摘要: We previously described an in vitro model which serous ovarian cystadenomas were transfected with SV40 large T antigen, resulting loss of RB and P53 functions thus mimicking genetic defects present early high-grade extra-uterine Mullerian (traditionally called ovarian) carcinomas including those associated the BRCA1 mutation carrier state. showed that replicative aging this cell culture leads to a mitotic arrest at spindle assembly checkpoint. Here we show is due reduction microtubule anchoring coincides decreased expression BUB1 kinase phosphorylated form its substrate, BUB3. The ensuing prolonged cohesion fatigue death or, cells recover from arrest, cytokinesis failure polyploidy. Down-regulation levels similar carriers increased uncontrolled kinetochore overcoming Progression anaphase under conditions formation chromatin bridges between chromosomal plates abnormal attachments kinetochore, significantly increasing risk failure. dependence scenario on accelerated can, least part, account for site specificity cancers state, as epithelia mammary gland reproductive tract are targets cell-nonautonomous consequences state cellular proliferation menstrual cycle progressions.