https://scholars.lib.ntu.edu.tw/handle/123456789/434988
標題: | Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis | 作者: | Tjiu J.-W. YI-HUA LIAO SUNG-JAN LIN Huang Y.-L. Tsai W.-L. CHIA-YU CHU Kuo M.-L. Jee S.-H. |
公開日期: | 2006 | 卷: | 126 | 期: | 5 | 起(迄)頁: | 1143-1151 | 來源出版物: | Journal of Investigative Dermatology | 摘要: | 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. ? 2006 The Society for Investigative Dermatology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-33646124246&doi=10.1038%2fsj.jid.5700191&partnerID=40&md5=4e719b6dd18fc9583804ffcc95d28779 https://scholars.lib.ntu.edu.tw/handle/123456789/434988 |
ISSN: | 0022-202X | DOI: | 10.1038/sj.jid.5700191 | SDG/關鍵字: | basic fibroblast growth factor; CD31 antigen; cyclooxygenase 2; matrigel; messenger RNA; protein bcl 2; protein mcl 1; small interfering RNA; vasculotropin A; angiogenesis; animal experiment; animal model; animal tissue; apoptosis; article; assay; basal cell carcinoma; cancer cell culture; carcinogenesis; cell structure; controlled study; DNA strand breakage; expression vector; flow cytometry; gene overexpression; genetic transfection; human; human cell; immunohistochemistry; metastasis; microvasculature; mouse; nonhuman; priority journal; prognosis; protein expression; protein secretion; SCID mouse; signal transduction; ultraviolet B radiation; Animals; Apoptosis; Carcinoma, Basal Cell; Cell Line, Tumor; Cyclooxygenase 2; Humans; Mice; Mice, SCID; Neovascularization, Pathologic; RNA, Messenger |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。