TY - JOUR
T1 - Role of AP-2 in tumor growth and metastasis of human melanoma
AU - Bar-Eli, Menashe
N1 - Funding Information:
I thank Dr. Judith P. Johnson for providing anti-MCAM/MUC18 antibody. Dr. K. Langley for antic-KIT antibody and Patherine Greenwood for expert preparation of this manuscript. This work was supported by NIH grant CA 76098.
PY - 1999
Y1 - 1999
N2 - 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, p21(WAF-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.
AB - 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, p21(WAF-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.
KW - Malignant melanoma
KW - Metastasis
KW - Transcription factor
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U2 - 10.1023/A:1006377309524
DO - 10.1023/A:1006377309524
M3 - Review article
C2 - 10721491
AN - SCOPUS:0033367565
SN - 0167-7659
VL - 18
SP - 377
EP - 385
JO - Cancer and Metastasis Reviews
JF - Cancer and Metastasis Reviews
IS - 3
ER -