Role of AP-2 in tumor growth and metastasis of human melanoma.
We previously demonstrated that expression of the cell surface adhesion molecule MCAM/MUC18 correlates directly with the metastatic potential of human melanoma cells. In addition, the progression of human melanoma towards the metastatic phenotype is associated with loss of expression of the tyrosine-kinase receptor c-KIT. This review summarizes our recent data demonstrating that the expression of both genes is regulated by the AP-2 transcription factor. Moreover, we have observed a loss of AP-2 expression in metastatic melanoma cells. Re-expression of AP-2 in the highly metastatic A375SM cells decreased their tumorigenicity and inhibited their metastatic potential in nude mice. MCAM/MUC18 mRNA and protein expression was significantly downregulated while c-KIT expression was upregulated in the AP-2 transfected cells. Since AP-2 also regulates other genes that are involved in the progression of human melanoma such as E-cadherin, MMP-2, p21WAF-1, HER-2, BCL-2, and insulin like growth factor receptor-1, we propose that loss of AP-2 is a crucial event in the development of malignant melanoma.
Bar-Eli
M
M
Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, USA. mbareli@notes.mdacc.tmc.edu
D000818:Animals; D015703:Antigens, CD; D051929:CD146 Antigen; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008545:Melanoma / Q000473:pathology* / Q000556:secondary; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D019006:Neural Cell Adhesion Molecules; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000502:physiology*
D015703:Antigens, CD; D051929:CD146 Antigen; D004268:DNA-Binding Proteins; C497902:MCAM protein, human; C497903:Mcam protein, mouse; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit