title: Modulation of autophagy in exJSRV-env-transfected cells through the Akt/mTOR and MAPK signaling pathway.
abstract: 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.
authors.affiliation: College of Veterinary Medicine, Inner Mongolia Agricultural University, Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, Hohhot 010018, China. Electronic address: yolo_1010@126.com.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Sun
authors.affiliation: College of Veterinary Medicine, Inner Mongolia Agricultural University, Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, Hohhot 010018, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Du
authors.affiliation: College of Veterinary Medicine, Inner Mongolia Agricultural University, Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, Hohhot 010018, China. Electronic address: liushuying@hotmail.com.
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D001343:Autophagy; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D015151:Immunoblotting; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D022141:Jaagsiekte sheep retrovirus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008168:Lung / Q000378:metabolism / Q000821:virology; D020935:MAP Kinase Signaling System; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011648:Pulmonary Adenomatosis, Ovine / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D012756:Sheep; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015686:Gene Products, env; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Autophagy; Envelope; Jaagsiekte sheep retrovirus; Ovine pulmonary adenocarcinoma; Signaling pathway