Modulation of autophagy in exJSRV-env-transfected cells through the Akt/mTOR and MAPK signaling pathway

• Published in: Biochemical and biophysical research communications Vol. 485; no. 3; pp. 672 - 678
• Main Authors: Sun, Xiaolin, Du, Fangyuan, Liu, Shuying
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.04.2017
• Subjects: Animals; Autophagy; Envelope; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibroblasts - metabolism; Fibroblasts - virology; Gene Products, env - genetics; Gene Products, env - metabolism; Host-Pathogen Interactions; Immunoblotting; Immunohistochemistry; Jaagsiekte sheep retrovirus; Jaagsiekte sheep retrovirus - genetics; Jaagsiekte sheep retrovirus - metabolism; Jaagsiekte sheep retrovirus - physiology; JNK Mitogen-Activated Protein Kinases - metabolism; Lung - metabolism; Lung - virology; MAP Kinase Signaling System; Mice; NIH 3T3 Cells; Ovine pulmonary adenocarcinoma; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Pulmonary Adenomatosis, Ovine - genetics; Pulmonary Adenomatosis, Ovine - metabolism; Pulmonary Adenomatosis, Ovine - virology; Sheep; Signaling pathway; TOR Serine-Threonine Kinases - metabolism; OPA; Jaagsiekte sheep retrovirus; Signaling pathway; Ovine pulmonary adenocarcinoma; Envelope; Env; Autophagy; JSRV
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.02.099

The envelope (Env) of Jaagsiekte sheep retrovirus (JSRV) is an oncoprotein of ovine pulmonary adenocarcinoma (OPA). Autophagy is involved in different cancers, but how it is carcinogenic in JSRV Env is unclear. Modulation of autophagy in exJSRV-env-NM-transfected cells through the Akt/mTOR and MAPK signaling pathway was studied, and we observed strong positive labeling of p-Akt, p-mTOR, p-MEK1/2, p-ERK1/2, p-p38 and p-JNK in tumor cells and typical type II pneumocytes in naturally infected OPA lung tissues, which was co-aligned with JSRV-Env positive cells as shown by immunohistochemical and microscopic analysis. Akt/mTOR and MAPK pathways were activated in OPA lung and JSRV-Env transfected NIH 3T3 cells. Decreased Beclin1 and LC3 II/I suggested that autophagy was inhibited in OPA lung and JSRV-Env transfected NIH 3T3 cells. Beclin1 and LC3 II/I increased in JSRV-Env transfected NIH3T3 cells treated with mTOR inhibitor (rapamycin), ERK1/2 inhibitor (PD 98059), p38 inhibitor (SB 203580) and JNK inhibitor (SP 600125), suggesting that Akt/mTOR and MAPK pathways were responsible for JSRV-Env decreased autophagy. In conclusion, JSRV Env decreased autophagy in JSRV-Env transfected NIH3T3 cells through Akt/mTOR and MAPK pathways, in particular, JNK and p38 pathways. •Phosphorylation of Akt/mTOR and MAPK pathways was aligned with JSRV-Env positive cells.•Akt/mTOR and MAPK pathways were activated in OPA lung and JSRV-Env transfected NIH 3T3 cells.•Beclin1 and LC3 II/I were decreased in OPA lung and JSRV-Env transfected NIH 3T3 cells.•Akt/mTOR and MAPK pathways were responsible for JSRV-Env decreased autophagy.