p38 MAP kinase plays a functional role in UVB-induced mouse skin carcinogenesis.

摘要: UVB irradiation of epidermal keratinocytes results in the activation p38 mitogen-activated protein kinase (MAPK) pathway and subsequently activator protein-1 (AP-1) transcription factor cyclooxygenase-2 (COX-2) expression. AP-1 COX-2 have been shown to play functional roles UVB-induced mouse skin carcinogenesis. In this study, experimental approach was express a dominant negative p38α MAPK (p38DN) epidermis SKH-1 hairless mice assess activation, expression, carcinogenesis response these compared wild-type littermates. We observed significant inhibition expression p38DN transgenic mice, leading reduction tumor number growth littermates chronic model. A potential mechanism for rate is an proliferation, as reduced Ki-67 staining wild-type. Although we detected no difference apoptotic rates between nontransgenic analysis acutely irradiated demonstrated that transgene significantly inhibited apoptosis keratinocytes. These counter concerns situation could compromise ability eliminate potentially tumorigenic cells. Our data indicate good target pharmacological intervention UV-induced cancer patients with sun damaged skin, suggest signaling reduces by inhibiting proliferation UVB-irradiated