title: Role of Pin1 in UVA-induced cell proliferation and malignant transformation in epidermal cells.
abstract: 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.
authors.affiliation: BK21 Project Team, College of Pharmacy, Chosun University, Gwangju 501-759, South Korea.
authors.forename: Chang Yeob
authors.initials: CY
authors.lastname: Han
authors.forename: Tran Thi
authors.initials: TT
authors.lastname: Hien
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Lim
authors.forename: Keon Wook
authors.initials: KW
authors.lastname: Kang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000096:biosynthesis; D004817:Epidermis / Q000201:enzymology* / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D051379:Mice; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: C530105:Ccnd1 protein, mouse; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D019938:Cyclin D1; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse; D000111:Acetylcysteine