Coexpression of p21Waf1/Cip1 and p53 in sun-exposed normal epidermis, but not in neoplastic epidermis.

Abstract

Wild-type p53 accumulation induced by DNA damaging agents such as ultraviolet (UV) radiation, gamma-irradiation and drugs, may arrest the cell cycle until DNA damage is repaired. p21Waf1/Cip1 is a cyclin-dependent kinase (CDK) inhibitor induced by wild-type p53. CDK is activated by cyclin and progresses the cell cycle. On the other hand, CDK inhibitors inhibit CDK activity to arrest the cell cycle. Thus, p21Waf1/Cip1 is thought to mediate the signal of p53 induced by DNA damaging agents to arrest the cell cycle. p21Waf1/Cip1 is induced by wild-type, but not mutant p53. To investigate p21Waf1/Cip1 regulation by p53 in epidermis in vivo, immunohistochemical staining of p21Waf1/Cip1 and p53 were conducted in chronically sun-exposed normal epidermis and in neoplastic epidermis, p21Waf1/Cip1 expression was found to be coincident with the p53-positive regions or not coincident with the p53-positive regions in chronically sun-exposed normal epidermis, whereas there was only low or undetectable p21Waf1/Cip1 expression in any regions including the p53-positive regions of solar keratosis and squamous cell carcinoma of the skin. This suggests that wild-type p53 and p21Waf1/Cip1 may play a part in chronically sun-exposed normal epidermis response to UV exposure, whereas p21Waf1/Cip1 cannot be induced by mutated p53 in solar keratosis and squamous cell carcinoma of the skin.