Epinephrine increases malignancy of breast cancer through p38 MAPK signaling pathway in depressive disorders

Objective: To uncover the possible mechanism and the effects of epinephrine on tumor growth in depression. Materials and methods: A chronic mild stress (CMS) model was employed to test the change of serum epinephrine levels in mice with depression. Tumor tissues and cell lines were analyzed to identify the molecular and cellular events influenced by depression in vitro. Results: The level of epinephrine was up-regulated in CMS mice serum. We found that beta-adrenergic receptors (beta-ARs) were expressed on MCF-7 and MDA-MB-231 breast cancer cells and that epinephrine enhanced the proliferation, migration, and invasion of breast cancer cells. Treatment of epinephrine increased the phosphorylation of p38 MAPK in cells and enhanced the growth of tumor in vivo. These two effects were significantly attenuated by propranolol (a beta-adrenergic receptor antagonist). Conclusions: These findings suggest that activation of epinephrine-induced p38 MAPK signaling pathway enhances the malignancy of breast cancer in depressive disorders. More effective psychological intervention might improve prognosis of cancer patients.