Expression of AP-2 transcription factor and of its downstream target genesc-kit, E-cadherin and p21 in human cutaneous melanoma

The AP-2 transcription factor plays a pivotal role in regulating the expres sion of several genes involved in tumor growth and progression of melanoma. We determined, by Western blot, variation in the level of expression of AP - and three of its downstream targets, c-kit, E-cadherin, and p21 in severa l human melanoma cell lines and, by immunohistochemistry, in a group of 99 histological samples including benign and malignant melanocytic lesions. A significant negative correlation between AP-2 expression level and tumor th ickness was found. Moreover, AP-2 expression was positively associated with E-cadherin and c-kit expression. In contrast, there was a significant nega tive association between AP-2 and p21 expression levels. These findings sug gest that p21 is independent of AP-2 transactivator function during the lat est phases of melanoma progression. Finally, AP-2, c-kit, E-cadherin, and p 21 expression levels did not show to be able to distinguish between dysplas tic nevi and nevi without dysplasia. We conclude that changes in the expres sion of these proteins are involved in the later phases of melanoma progres sion, and may be responsible for the transition from local invasive melanom a to metastasis. J. Cell. Biochem. 83: 364-372, 2001. (C) 2001 Wiley-Liss, Inc.