title: Net expression inhibits the growth of pancreatic ductal adenocarcinoma cell PL45 in vitro and in vivo.
abstract: Pancreatic ductal adenocarcinoma has a poor prognosis due to late diagnosis and a lack of effective therapeutic options. Thus, it is important to better understand its molecular mechanisms and to develop more effective treatments for the disease. The ternary complex factor Net, which exerts its strong inhibitory function on transcription of proto-oncogene gene c-fos by forming ternary complexes with a second transcription factor, has been suspected of being involved in pancreatic cancer and other tumors biology. In this study, we found that the majority of pancreatic ductal adenocarcinoma tissues and cell lines had weak or no expression of Net, whereas significantly high level of Net expression occurred in paired adjacent normal tissues we studied. Furthermore, using in vitro and in vivo model systems, we found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. Our data thus suggested that Net might play an important role in pancreatic carcinogenesis, possibly by acting as a tumor suppressor gene.
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Baiwen
authors.initials: B
authors.lastname: Li
authors.forename: Xinjian
authors.initials: X
authors.lastname: Wan
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Zeng
authors.forename: Duanmin
authors.initials: D
authors.lastname: Hu
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Qian
authors.forename: Lungen
authors.initials: L
authors.lastname: Lu
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Meng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C000715470:MAS1 protein, human; D050484:Norepinephrine Plasma Membrane Transport Proteins; D000090063:Proto-Oncogene Mas; C493227:SLC6A2 protein, human; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4