Expression of AP-2 transcription factor and of its downstream target genes c-kit, E-cadherin and p21 in human cutaneous melanoma.
The AP-2 transcription factor plays a pivotal role in regulating the expression of several genes involved in tumor growth and progression of melanoma. We determined, by Western blot, variation in the level of expression of AP-2 and three of its downstream targets, c-kit, E-cadherin, and p21 in several 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 thickness was found. Moreover, AP-2 expression was positively associated with E-cadherin and c-kit expression. In contrast, there was a significant negative association between AP-2 and p21 expression levels. These findings suggest that p21 is independent of AP-2 transactivator function during the latest phases of melanoma progression. Finally, AP-2, c-kit, E-cadherin, and p21 expression levels did not show to be able to distinguish between dysplastic nevi and nevi without dysplasia. We conclude that changes in the expression of these proteins are involved in the later phases of melanoma progression, and may be responsible for the transition from local invasive melanoma to metastasis.
Baldi
A
A
Laboratory of Cell Metabolism and Pharmacokinetics, Center for Experimental Research, Regina Elena Cancer Institute, Rome, Italy.
Santini
D
D
Battista
T
T
Dragonetti
E
E
Ferranti
G
G
Petitti
T
T
Groeger
A M
AM
Angelini
A
A
Rossiello
R
R
Baldi
F
F
Natali
P G
PG
Paggi
M G
MG
D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis*; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000378:metabolism*; D009506:Nevus / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; D015820:Cadherins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit