Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis

J Invest Dermatol. 2006 May;126(5):1143-51. doi: 10.1038/sj.jid.5700191.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Carcinoma, Basal Cell / blood supply
  • Carcinoma, Basal Cell / enzymology*
  • Carcinoma, Basal Cell / etiology
  • Carcinoma, Basal Cell / pathology
  • Cell Line, Tumor
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / physiology*
  • Humans
  • Mice
  • Mice, SCID
  • Neovascularization, Pathologic / etiology*
  • RNA, Messenger / analysis


  • RNA, Messenger
  • Cyclooxygenase 2