Coexpression of p21Waf1/Cip1 and p53 in sun-exposed normal epidermis, but not in neoplastic epidermis.
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.
Inohara
S
S
Department of Dermatology, Hyogo College of Medicine, Japan.
Kitagawa
K
K
Kitano
Y
Y
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002453:Cell Cycle; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004817:Epidermis / Q000378:metabolism* / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D007642:Keratosis / Q000378:metabolism; D008875:Middle Aged; D012878:Skin Neoplasms / Q000378:metabolism*; D013472:Sunlight
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins