Induced expression of p16 and p21 proteins in UVB-irradiated human epidermis and cultured keratinocytes

It has been suggested that p16INK4a, the product of the cyclin-dependent kinase inhibitor 2 or multiple tumor suppressor 1 gene, prevents phosphorylation of the retinoblastoma gene product, and thus acts as a negative cell cycle regulator. To elucidate an effect of ultraviolet B (UVB) radiation on p16 expression and its relation to p21, and proliferating cell nuclear antigen (PCNA), immunohistochemical and western blot analyses were performed on WE-irradiated normal human epidermis and cultured keratinocytes, respectively. Little p16 protein was seen in the control epidermis or keratinocytes. Increases in the levels of p16 protein in both WE-irradiated epidermis and keratinocytes occurred in a similar manner, in which p16 was induced at 24-48 h and peaked at 72-120 h after irradiation. The induced expression of p21 was observed relatively earlier than that of p16, with peaked expression at 24-48 h and a return to control level by 168 h. PCNA expression was increased slightly until 48 h but significantly increased during 48-168 h of post-irradiation with peak expression at 72 h. These results indicate that together with p21, p16 protein may play an important role for protective or adaptive response to WB exposure of human skin. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.