Role of Pin1 in UVA-induced cell proliferation and malignant transformation in epidermal cells

• Published in: Biochemical and biophysical research communications 2011-06, Vol.410 (1), p.68-74
• Main Authors: Han, Chang Yeob, Hien, Tran Thi, Lim, Sung Chul, Kang, Keon Wook
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; ANIMAL TISSUES; Animals; BIOLOGICAL RADIATION EFFECTS; Cell Line; CELL PROLIFERATION; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Cyclin D1; Cyclin D1 - biosynthesis; Epidermis - enzymology; Epidermis - pathology; Epidermis - radiation effects; EPITHELIOMAS; Humans; INHIBITION; IRRADIATION; MICE; NIMA-Interacting Peptidylprolyl Isomerase; OXIDIZERS; Peptidylprolyl Isomerase - genetics; Peptidylprolyl Isomerase - physiology; Pin1; Proliferation; PROTEINS; RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; Reactive Oxygen Species - metabolism; SKIN; Skin cancer; Skin Neoplasms - enzymology; Skin Neoplasms - etiology; Skin Neoplasms - pathology; Transcription Factor AP-1 - metabolism; Transformation; TRANSFORMATIONS; Ultraviolet Rays; UVA
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.05.106

► Pin1 expression is enhanced by low energy UVA irradiation in both skin tissues of hairless mice and JB6 C141 epidermal cells. ► UVA irradiation increases activator protein-1 activity and cyclin D1 in a Pin1-dependent manner. ► UVA potentiates EGF-inducible, anchorage-independent growth of epidermal cells, and this is suppressed by Pin1 inhibition or by anti-oxidant. Ultraviolet A (UVA) radiation ( λ = 320–400 nm) is considered a major cause of human skin cancer. Pin1, a peptidyl prolyl isomerase, is overexpressed in most types of cancer tissues and plays an important role in cell proliferation and transformation. Here, we demonstrated that Pin1 expression was enhanced by low energy UVA (300–900 mJ/cm 2) irradiation in both skin tissues of hairless mice and JB6 C141 epidermal cells. Exposure of epidermal cells to UVA radiation increased cell proliferation and cyclin D1 expression, and these changes were blocked by Pin1 inhibition. UVA irradiation also increased activator protein-1 (AP-1) minimal reporter activity and nuclear levels of c-Jun, but not c-Fos, in a Pin1-dependent manner. The increases in Pin1 expression and in AP-1 reporter activity in response to UVA were abolished by N-acetylcysteine (NAC) treatment. Finally, we found that pre-exposure of JB6 C141 cells to UVA potentiated EGF-inducible, anchorage-independent growth, and this effect was significantly suppressed by Pin1inhibition or by NAC.