PGC1 alpha expression and correlation with BRAF mutational status

PP-7 PGC1 alpha expression and correlation with BRAF mutational status I. Maida1 , A. Ferretta1 , T. Cocco1 , P. Zanna1 , R. Labarile1 , S. Guida3 , C. Grieco1 , L. Porcelli2 , A. Azzariti2 , S. Tommasi2 , A. Albano2 , S. Strippoli2 , M. Guida2 , R. Filotico3 , G. Guida1 1 Department of Basic Medical Sciences, Neurosciences and Sense Organs, School of Medicine, University of Bari, Bari, Italy; 2 Clinical Experimental Oncology Laboratory and Medical Oncology Department, National Cancer Institute, Bari, Bari, Italy; 3 Unit of Dermatology and Venereology, University of Bari, P.O. “A. Perrino”, Brindisi, Italy In this study we present the behaviour of the mitochondrial master regulator gene PGC1alpha in novel sporadic melanoma cell lines. The HBL and LND1 cell lines, wild type for BRAF, highly express PGC1alpha while hmel1, hmel9, hmel11, Mba72, M3, presenting BRAF mutations at the V600 residue, show a down regulation of this gene. Mutations in homo and/or heterozigosis of V600 in BRAF protein kinase always correspond to a down regulation of PGC1alpha as described for the cell lines A375, SKmel28, SKmel2, RPM7951, WM115 in Vasquez et al., 2013. MITF expression levels, measured by western blotting in our melanoma cell lines, were more abundant in HBL and LND1 cell lines with respect to the other cell lines harbouring BRAF mutations. There is a direct correspondence between PGC1alpha and MITF levels: higher levels of PGC1alpha are associated with an enhanced MITF quantity. The analysis of cAMP levels in our melanoma cell lines showed a similar trend, being higher in wt BRAF cell lines compared to the other cell lines. Our data confirm the key role of BRAF mutations, MITF and cAMP levels in melanoma biology, suggesting a very important association with the transcriptional co-activator PGC1alpha, involved in energy metabolism, in mitochondrial biogenesis but also in various physiological stimuli which are reprogrammed in melanoma cells. This factor, also involved in regulating angiogenetic mechanisms, could be an interesting gene for target therapy but also it could provide an important diagnostic role.