title: Pim-3 promotes the growth of human pancreatic cancer in the orthotopic nude mouse model through vascular endothelium growth factor.
abstract: BACKGROUND
  As one of the most lethal cancers, pancreatic cancer presents poor prognosis with an overall 5-y survival of less than 5%. We previously reported that Pim-3, a member of the proto-oncogene Pim family that encodes serine/threonine kinases, is aberrantly expressed in human pancreatic cancer lesions. In the current study, we investigated the role of Pim-3 in promoting tumor growth and angiogenesis in an orthotopic nude mouse model of human pancreatic cancer.
  
  
  METHODS
  We constructed retroviral vectors for human Pim-3 and a kinase-dead mutant of human Pim-3 (K69M); the retroviral supernatants generated from these vectors were then used to infect the human pancreatic cancer cell line MiaPaCa-2 to establish stable cell lines. We assessed cell proliferation using CCK-8, tumor growth, and angiogenesis in vivo in an orthotopic mouse model of pancreatic cancer. While tumor size was measured using magnetic resonance imaging, the tumor tissues were excised for protein extraction and histological analysis to detect vascular endothelium growth factor (VEGF) expression and vessel density.
  
  
  RESULTS
  We established an orthotopic nude mouse model of human pancreatic cancer. We observed that Pim-3 promoted the proliferation of human pancreatic cancer cells, both in vitro and in vivo. Moreover, Pim-3 is required for vasculogenesis of primary human pancreatic tumors in vivo and promotion of angiogenesis through the induction of VEGF expression.
  
  
  CONCLUSIONS
  Pim-3 can promote tumor growth and angiogenesis by stimulating the VEGF pathway.
authors.affiliation: Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Sheng
authors.initials: S
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C499249:PIM3 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Nude mice orthotopic model; Pim-3; VEGF