title: Upregulation of the expression of Wnt5a promotes the proliferation of pancreatic cancer cells in vitro and in a nude mouse model.
abstract: Wnt proteins are a group of secreted signaling proteins, which function to regulate cell fate and pattern formation during embryogenesis. Altered expression of Wnt5a has been implicated in human carcinogenesis and tumor progression. A previous study identified that Wnt5a is overexpressed in human pancreatic cancer tissues, and that upregulated expression of Wnt5a promotes tumor cell migration and invasion. The present study investigated the role of Wnt5a in pancreatic cancer cell proliferation in vitro and in an orthotopic nude mouse model. Wnt5a cDNA or small interfering RNA were stably transfected into pancreatic cancer cells to assess cell proliferation-associated behaviors, including cell viability, colony formation and apoptosis in vitro, as well as tumor cell growth in an orthotopic nude mouse model. Western blot analysis was used to analyze the expression of Wnt signaling molecules. The data showed that upregulation of the expression of Wnt5a significantly promoted proliferation of the human pancreatic cells, but inhibited tumor cell apoptosis in vitro and promoted tumor growth in an orthotopic nude mouse model. By contrast, knockdown of the expression of Wnt5a inhibited cell growth and promoted apoptosis of the pancreatic cancer cells. The data also revealed that β-catenin mediated the effects of Wnt5a on the regulation of pancreatic cancer cell apoptosis in vitro. These results suggested that Wnt5a is involved in the modulation of pancreatic cancer cell proliferation, and that Wnt5a may be a potential target for pancreatic cancer therapy.
authors.affiliation: Department of Pathology, No. 455 Hospital of PLA, Shanghai 200052, P.R. China.
authors.forename: Haiji
authors.initials: H
authors.lastname: Bo
authors.affiliation: Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin