Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes

The effects of p38 MAP kinase and ERK on UVB induced c-fos gene expression were studied in a human keratinocyte cell line, FL30, UVB significantly inc reased c-fos gene expression at both the transcriptional and protein le,els . p38 and ERK were also significantly activated after UVB irradiation. Trea ting the cells with p38 inhibitor SB202190 inhibited p38 activation, but no t ERK; treating the cells with MEK-1 inhibitor PD98059 inhibited ERK activa tion without suppressing p38 activation, The kinase activation was determin ed by Western blots using phospho-p38 or ERK antibodies, or an in vivo p38 activity assay. Further studies demonstrated that blocking p38 almost compl etely abrogated UVB induced c-fos gene transcription and c-Fos protein synt hesis. Inhibiting ERK partially abrogated UVB induced c-fos transcriptional and protein levels, Suppression of both p38 and ERK not only completely bl ocked UVB induced c-fos expression, but also decreased c-fos gene basal exp ression. Our data indicated that p38 may play a more important role than ER K in UVB induced c-fos expression in human keratinocytes, Since c-fos expre ssion may play an important role in UVB induced AP-1 activation, and AP-1 a ctivation is known to play a role in tumor promotion, both p38 and ERK coul d be potential targets for chemoprevention of skin cancer.