Wild type BRCA2 restores chromosomal stability and cytokinesis in the tumor cells harboring a rare BRCA2 allele
BRCA2 mutations predispose individuals to breast, ovarian, and other cancers. BRCA2 involved in regulation of some cellular processes and it’s deficiency is associated with genomic instability and abnormal cytokinesis. We observed that the breast cancer cell line MX1 is genomically unstable and shows abnormal cytokinesis. Fluorescent in situ hybridization (FISH) analysis revealed that the cell line harbors only one allele of the BRCA2 gene. As a result of mutation analysis we identified that the allele has four missense SNPs. Further, we found that the protein is expressed at a very low level in comparison with 10 randomly picked breast cancer cell lines. To examine whether the phenotype could be rescued by BRCA2 we generated a stable cell line that expresses the wild-type allele in the MX1 cells. The expression of the protein restored chromosomal stability and cytokinesis. Our results also support the observations that BRCA2 is a regulator for the S-G2 cell cycle progression and cell growth control.
The obtained data demonstrate that severe genomic instability due to BRCA2 deficiency could be successfully rescued by the expression of the wild type allele. We also address a question whether the described missence substitutions could modify the risk of cancer.