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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-4-18
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-202X
pubmed:author
pubmed:issnType
Print
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1143-51
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis.
pubmed:affiliation
Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't