Activation of cAMP signaling system increases BRMS1 and reduces cellular migration

Abstract

BRMS1 (breast cancer metastasis suppressor 1) is a tumor suppressor gene that is involved in metastatic progress of breast cancer cells, lung cancer cells and melanoma. BRMS1 has shown a significant effect on cell migration when overexpressed and silenced by siRNA, but its mechanism of regulation is unclear. Thus, we have investigated the effect of cAMP signaling system on the expression of BRMS1 and its underlying mechanism in non-small cell lung cancer (NSCLC) cells. Treatment with isoproterenol increased mRNA and protein expressions of BRMS1 and the activity of BRMS1 promoter in H1299 NSCLC cells. Isoproterenol-induced BRMS1 promoter activity and its protein expression were obstructed by inhibition of PKA with dominant negative PKA and H89. Decoy CRE transfection also halted the isoproterenol-induced BRMS1 promoter activity. Isoproterenol treatment resulted in considerably less migration while transfection of siRNA against BRMS1 abolished the effect. It is concluded that activation of cAMP signaling system causes up-regulation of BRMS1 mRNA and protein in a PKA-CREB dependent pathway and reduces cellular migration in NSCLC cells.