XAF1 expression is significantly reduced in human melanoma.

Deregulation of apoptotic processes is likely one of the key factors contributing to the malignant nature of melanoma marked by strong chemoresistance. X-linked inhibitor of apoptosis protein (XIAP) suppresses apoptosis through the inhibition of various caspases. Recently, XIAP-associated factor 1 (XAF1) has been identified as a XIAP-binding protein that antagonizes the anti-apoptotic activity of XIAP. In this study, we sought to determine the role of XAF1 in melanoma progression. Analysis of XAF1 mRNA expression in melanoma cell lines revealed that XAF1 mRNA was downregulated in 15 of 16 cell lines examined. We next evaluated XAF1 protein expression on a tissue microarray representing 40 benign nevi and 70 primary melanomas. Our results showed that XAF1 expression in melanoma tissues was significantly reduced compared with benign melanocytic nevi (p<0.05). Our data also demonstrated that the substantial reduction of XAF1 expression occurred in both nucleus and cytoplasm in the tumor cells (p<0.0001 for both). Reduced XAF1 expression, however, was not significantly correlated with tumor thickness and 5-y patient survival. Further studies are required to understand the molecular mechanisms governing the selective loss of XAF1 expression in the tumor tissue.