These findings enhance our understanding of how loss of BRCA1 disrupts mitosis regulation through dysregulation of cyclin B1 and provide evidence suggesting that targeting cyclin B1 may be useful in BRCA1-associated breast cancer therapy.
Functional assays revealed reduced proliferation (p<0.05) and decreased Cyclin B1 protein levels following transfection of breast cancer cells with miR-379.
For CCNB1, rs2069429 was significantly associated with increased BC susceptibility under recessive model (OR=2.352, 95%CI=1.480-3.737), so was the diplotype TAGT/TAGT (OR=1.947 95%CI=1.154-3.284, P=0.013).
The antiproliferative effects of FHL3 on breast cancer cell growth were associated with both the G1 and the G2/M cell cycle arrest, which was accompanied by a marked inhibition of the G1-phase marker cyclin D1 and the G2/M-phase marker cyclin B1 as well as the induction of the cyclin dependent kinase inhibitor p21 (WAF1/CIP1), a negative regulator of cell cycle progression at G1 and G2.
DIM inhibited the breast cancer cell growth in vitro and in vivo, and caused cell-cycle arrest by down-regulating protein levels of cell-cycle related kinases CDK1, CDK2, CDK4, and CDK6, as well as Cyclin B1 and Cdc25A.
Although CCNE1 was present in significantly higher copy numbers in basal-like versus other subtypes (ANOVA P < 0.001), CCNB1 gene copy number did not show gain in breast cancer.
We evaluate C-5 propyne pyrimidine modified phosphorothioate antisense oligonucleotides (ONs) targeted against two human cell cycle proteins that are aberrantly expressed in breast cancer: p34cdc2 kinase and cyclin B1.