Keiko Kitagawa

Expression of Cyclin D1 and p53 Protein in Various Malignant Skin Tumors

BACKGROUND Overexpression of cyclin D1 and p53 protein has been reported in many types of malignant tumors. OBJECTIVES We investigated whether cyclin D1 was detected immunohistochemically in various types of malignant tumors of the skin, comparable with p53 protein. METHODS Immunohistochemical staining of cyclin D1 and p53 protein was applied to squamous cell carcinoma, malignant melanoma and malignant fibrous histiocytoma and various kinds of benign skin tumors. RESULTS Cyclin D1 was positive only in malignant tumors at the same incidence as p53 protein. CONCLUSION Cyclin D1 immunohistochemical staining may be a malignant marker for various skin tumors.

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

Summary Wild‐type p53 accumulation induced by DNA damaging agents such as ultraviolet (UV) radiation. γ‐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.

Cell cycle regulators in the keratinocyte (cyclin-cdk)

Abstract It has recently become clear that cyclin‐dependent kinase (cdk) complex regulates the cell cycle by phosphorylating Rb protein, a tumor suppressor protein. It is likely that this complex is a target of various growth factors and anti‐growth factors (UV TGF‐β etc.) in keratinocyte (KC). It has also been suggested that abnormalities in the cell cycle regulating mechanism such as increased activity of cyclin‐cdk due to mutation of p53, a tumor suppressor gene, and overexpression of cyclin D may be concerned with carcinogenesis of KC. Thus, recent studies indicate that the cyclin‐cdk complex is a common target of proliferation and carcinogenesis in KC.