G-protein coupled receptor (GPCR) signaling, predominantly the cyclic AMP (cAMP) signaling, is crucial for melanocyte proliferation and differentiation. Previous studies have shown a downregulation in cAMP signaling in mutant NRAS melanoma. However, no relationship has been reported about cAMP signaling in mutant BRAF melanoma, which makes up about 60% of all cutaneous melanoma. Here, we studied the role of four main G-protein signaling pathways using reporters for Gαs (cAMP Response Element, CRE), Gαq (inositol triphosphate signaling, NFAT-RE), Gα12 (RhoA signaling, SRF-RE) and Gβγ (MAPK pathway, SRE), in melanoma. Our data show that cAMP signaling is substantially more constitutively active in BRAFV600E mutant melanoma than NRAS mutant melanoma. Moreover, hyperactivation of cAMP signaling decreases proliferation and migration in BRAFV600E. Interestingly, in a melanoma cell line with neither BRAF nor NRAS mutation, cAMP hyperactivation increased proliferation. Furthermore, BRAFV600E inhibition increases constitutive cAMP activity. These results show a possible crosstalk between cAMP signaling and BRAFV600E in melanoma.

Citation Format: Carlos I. Rodriguez. cAMP signaling in BRAFV600E melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4198. doi:10.1158/1538-7445.AM2014-4198

©2014 American Association for Cancer Research.
2014