Involvement of nuclear factor of activated T cells 3 (NFAT3) in cyclin D1 induction by B[a]PDE or B[a]PDE and ionizing radiation in mouse epidermal Cl 41 cells.

The results from animal studies have shown that mouse skin is highly susceptible to both ionizing radiation and benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE). Previous studies have also indicated that cyclin D1 plays a crucial role in controlling cell proliferation and tumorigenesis. We, therefore, investigated here the effect of ionizing radiation and B[a]PDE on cyclin D1 transcription and potential involvement of NFAT3 in regulation of cyclin D1 transcription in mouse epidermal Cl 41 cells. We found that B[a]PDE exposure induced a high level of NFAT activation and cyclin D1 transcription in mouse epidermal Cl 41 cells. Ionizing radiation exhibited an enhancement for NFAT activation and cyclin D1 induction by B[a]PDE, even though ionizing radiation by itself had only a marginal effect. By stably knockdown of NFAT3 protein expression using specific NFAT3 small interfering RNA (siRNA), we found that cyclin D1 induction by B[a]PDE or B[a]PDE plus ionizing radiation was dramatically impaired. These results indicate that ionizing radiation is able to enhance cyclin D1 transcription induced by B[a]PDE, and NFAT3 is involved in the regulation of cyclin D1 transcription by B[a]PDE or B[a]PDE plus ionizing radiation.