Inhibition of Cancer Cell Growth by BRCA2

The breast cancer susceptibility gene BRCA2 has been suggested to function as a "caretaker" of the genome. Cells without wild-type BRCA2 are deficient in repairing DNA damage. However, whether BRCA2 can also suppress oncogenesis by regulating cell proliferation remains to be determined. To address this question, the expression of wild-type BRCA2 protein was reconstituted, in an either constitutive or regulated manner, in the pancreatic cancer cell line Capan-1, which expresses only a mutant BRCA2. Expression of wild-type BRCA2 inhibited cell proliferation in culture and suppressed tumor growth in animals. Our results showed that, in addition to the DNA repair function, BRCA2 also suppresses tumor development by inhibiting cancer cell growth.