title: Upregulation of the splice variant MUC4/Y in the pancreatic cancer cell line MIA PaCa-2 potentiates proliferation and suppresses apoptosis: new insight into the presence of the transcript variant of MUC4.
abstract: MUC4/Y, the transcript variant 4 of MUC4, lacks exon 2 as compared with the transcript variant 1 of MUC4. To date, direct evidence for the function of MU4/Y remains to be reported. Previous studies based their hypotheses regarding the function of MUC4/Y on the characteristic structure domains of this variant. The aim of the present study was to investigate the specific function of MUC4/Y. The pancreatic cancer cell line MIA PaCa-2 with low MUC4/Y expression was used to establish a stable cell model of MUC4/Y upregulation using a lentivirus vector system. Results showed that MUC4/Y anchored on the cytomembrane and affected cell morphology and cell cycle. Functional analyses indicated that MUC4/Y upregulation slightly potentiated cell proliferation and significantly suppressed apoptosis both in vivo and in vitro. Further studies revealed that the JNK and AKT signalling pathways were activated. Meanwhile, MUC4/Y upregulation elicited minimal effect on the phosphorylation level of HER2, a membrane partner of MUC4. These results suggest that MUC4/Y promotes tumour progression through its anti-apoptotic and weak mitogenic effect on MIA PaCa-2 cells.
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Kunling
authors.initials: K
authors.lastname: Xie
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhi
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Zekuan
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055264:Mucin-4 / Q000096:biosynthesis / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D055264:Mucin-4; D020033:Protein Isoforms; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C524658:MUC4 protein, human; C508053:ERBB2 protein, human