The cross-talk between cAMP and ERK1/2 pathway has been implicated in the proliferation of somatotropinomas. Both B-Raf and C-Raf are intricately involved in the cross-talk depending on cell-type specificity, however, it has not been illustrated in somatotropinomas. This study aimed to figure out the role of B-Raf and C-Raf in the proliferation of somatotropinomas mediated by the cross-talk. By employing human sommatotroph cells and a rat cell line (GH3), selective inhibitors of B- and C-Raf and knockdown with siRNAs were used in conjunction with forskolin to investigate effects on cell proliferation. In addition, effects on phosphorylation of ERK1/2 and CREB, levels of cyclinsD1 and D3, B-Raf and C-Raf activity, together with B-Raf/C-Raf binding were determined. Elevation of cAMP by exogenously added forskolin exerts significant stimulatory effects on somatotroph proliferation. Moreover, forskolin induced phosphorylation of ERK1/2 and CREB, and increased levels of cyclinsD1 and D3. These effects were attenuated by B-Raf and C-Raf inhibitors and by specific knockdown with siRNAs. Forskolin elevated B-Raf and C-Raf activity, and both molecules are not heterodimerized in somatotrophs. Results indicate that cAMP promotes proliferation of tumorous somatotrophs via cross-talk with the ERK1/2 pathway in a B-Raf and C-Raf dependent manner. In particular, heterodimerizationof B-Raf and C-Raf does not appear to be necessary in this mechanism in somatotrophs.