title: Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis.
abstract: Cyclooxygenase-2 (COX-2) is critical for tumor formation, angiogenesis, metastasis, and prognosis. In this study, the role of COX-2 in antiapoptosis, tumorigenesis, and angiogenesis of human basal cell carcinoma (BCC) cells was investigated. Transfection of COX-2 constitutive expression vector into a BCC cell line yielded several overexpressing clones. All transfectants demonstrated remarkable resistance to ultraviolet B-induced apoptosis (confirmed by flow cytometry analysis, morphological change, and DNA fragmentation). Immunoblot analysis revealed marked increases in apoptosis-regulated genes Mcl-1 and Bcl-2. A 10-fold concentrated conditioned medium from COX-2-overexpressing BCC cells exhibited higher angiogenic activity in Matrigel plug and human umbilical vein endothelial cell tube formation assay. Cells exhibited increased levels of vascular endothelial growth factor-A (VEGF-A) mRNA and protein, and secreted VEGF-A and basic fibroblast growth factor (bFGF). COX-2-specific small interfering RNA markedly reduced the secreted species. After 7 weeks of inoculation, the tumor volume of COX-2-overexpressing cells in severe combined immunodeficient mice was significantly greater than that of vector control cells. Immunohistochemical analysis of CD31-positive vessels revealed a two-fold increase in microvessel density in COX-2 tumors, compared to control vector tumors. Our data indicate that Mcl-1 and Bcl-2, as well as VEGF-A and bFGF, are downstream effectors of COX-2-induced antiapoptosis and angiogenesis, respectively.
authors.affiliation: Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei, Taiwan.
authors.forename: Jeng-Wei
authors.initials: JW
authors.lastname: Tjiu
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Liao
authors.forename: Sung-Jan
authors.initials: SJ
authors.lastname: Lin
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Huang
authors.forename: Wei-Ling
authors.initials: WL
authors.lastname: Tsai
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Chu
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.forename: Shiou-Hwa
authors.initials: SH
authors.lastname: Jee
mesh_terms: D000818:Animals; D017209:Apoptosis; D002280:Basal Cell Carcinoma / Q000098:blood supply / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D051546:Cyclooxygenase 2