Gene 33 mediates Cr(VI)-induced DNA damage response

Hexavalent chromium [Cr(VI)] is a known human lung carcinogen. But, the molecular players that mediate its carcinogenesis are poorly defined. Gene 33 (Mig-6, ERRFI1) is an adaptor protein implicated in lung cancer. It regulates multiple signaling pathways mediating cell proliferation, migration, apoptosis, and senescence. In this study, we found that Cr(VI) triggers a typical DNA damage response in BEAS-2B lung epithelial cells, manifested as elevation of γH2AX and P-p53(S15) levels, in a dose-dependent fashion. The Cr(VI)-induced DNA damage response appeared mainly in the S and G2/M phases of the cell cycle. However, the dose-dependent increase in the γH2AX level was more pronounced in G1 and S phases than in the G2/M phase. In contrast, P-p53(S15) signals changed more uniformly in all phases of the cell cycle. Cr(VI) also induced the DNA damage response in A549 lung carcinoma cells. Gene 33 knockdown with siRNA significantly inhibited Cr(VI)-induced γH2AX signals in A549. More interestingly, inhibition ...