title: β2-adrenergic receptor activation promotes the proliferation of A549 lung cancer cells via the ERK1/2/CREB pathway.
abstract: Lung cancer is one of the most common cancers worldwide and accounts for 28% of all cancer-related deaths. The expression of the β2‑adrenergic receptor (β2‑AR), one of the stress‑inducible receptors, has been reported to be closely correlated with malignant tumors. However, the role of β2‑AR activation in human lung epithelial‑derived cancer A549 cells and the underlying mechanisms are not fully understood. In the present study, we found that activation of β2‑AR but not β1‑AR promoted the proliferation of A549 cells. Isoproterenol (ISO) stimulation of β2‑AR induced extracellular signal‑regulated kinase 1/2 (ERK1/2) and cyclic adenosine monophosphate response element‑binding protein (CREB) phosphorylation. Blocking the ERK1/2 pathway by U0126 inhibited CREB phosphorylation and also suppressed A549 cell proliferation. Moreover, ISO treatment enhanced the expression of matrix metalloproteinase (MMP) family proteins such as MMP‑2, MMP‑9, and also vascular endothelial growth factor (VEGF), which were able to be blocked by knockdown of CREB. In conclusion, our data revealed that β2‑AR induced ERK1/2 phosphorylation which in turn activated CREB to promote A549 cell proliferation. These findings elucidate potential therapeutic targets for lung cancer treatment.
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330001, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330001, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: He
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330001, P.R. China.
authors.forename: Shiling
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330001, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Life Science, Nanchang University, Nanchang, Jiangxi 330001, P.R. China.
authors.forename: Bingxing
authors.initials: B
authors.lastname: Pan
authors.affiliation: Institute of Life Science, Nanchang University, Nanchang, Jiangxi 330001, P.R. China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016133:Polymerase Chain Reaction; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D018343:Receptors, Adrenergic, beta-2