Cells that compensate for the resulting loss of DNA repair function by increasing RAD51 levels are prone to tumor formation, according to Cancer Research paper.
Pathway that compensates for the DNA repair function lost in cells lacking BRCA1 may function abnormally leading to breast cancer, according to scientists from the University of Chicago and Kyoto University.
“If you take a normal, healthy cell and get rid of BRCA1, you end up with an unhealthy, slow-growing cell,” explains Douglas Bishop, Ph.D., associate professor of radiation and cellular oncology at Chicago and principal investigator of the study. “That’s a bit of a paradox, because loss of BRCA1 also causes tumors, and tumor formation is not normally associated with poor cell growth.”
The team examined genomic data from 117 primary breast tumors for evidence of elevated levels of RNA for genes involved in homologous recombination. They found that the level of RNA for three genes—RAD51, a DNA repair protein involved in homologous recombination, and two of its key accessory factors—was significantly higher in BRCA1-deficient tumors compared with breast tumors that were not associated with BRCA1 mutations.
When the researchers took normal, healthy cells in culture and disabled the BRCA1 gene, the cells survived but grew slowly and were unable to repair DNA damage normally. When the investigators increased the amount of RAD51 in these cells, however, the ability of cells to repair DNA damage was restored and the mutated cells grew more quickly.
“BRCA1-deficiency by itself would probably not cause a tumor,” Dr. Bishop notes, “but cells that manage to compensate for the BRCA1 defect in repair by ramping up RAD51 levels are likely to be less genetically stable than normal cells and therefore more prone to form tumors.”
The study is published in the October 15 issue of Cancer Research.
