title: Modulation of pancreatic tumor potential by overexpression of protein kinase C β1.
abstract: OBJECTIVE
  This study aimed to investigate whether the overexpression of protein kinase C β1 (PKCβ1) is able to modulate the malignant phenotype displayed by the human ductal pancreatic carcinoma cell line PANC1.
  
  
  METHODS
  PKCβ1 overexpression was achieved using a stable transfection approach. PANC1-PKCβ1 and control cells were analyzed both in vitro and in vivo.
  
  
  RESULTS
  PANC1-PKCβ1 cells displayed a lower growth capacity associated with the down-regulation of the MEK/ERK pathway and cyclin expression. Furthermore, PKCβ1 overexpression was associated with an enhancement of cell adhesion to fibronectin and with reduced migratory and invasive phenotypes. In agreement with these results, PANC1-PKCβ1 cells showed an impaired ability to secrete proteolytic enzymes. We also found that PKCβ1 overexpressing cells were more resistant to cell death induced by serum deprivation, an event associated with G0/G1 arrest and the modulation of PI3K/Akt and NF-κB pathways. Most notably, the overexpression of PKCβ1 completely abolished the ability of PANC1 cells to induce tumors in nude mice.
  
  
  CONCLUSIONS
  Our results established an important role for PKCβ1 in PANC1 cells suggesting it would act as a suppressor of tumorigenic behavior in pancreatic cancer.
authors.affiliation: From the *Research Area, Institute of Oncology "Angel H. Roffo," University of Buenos Aires, Buenos Aires, Argentina; and †Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Stéfano M
authors.initials: SM
authors.lastname: Cirigliano
authors.forename: Laura V
authors.initials: LV
authors.lastname: Mauro
authors.forename: Valeria C
authors.initials: VC
authors.lastname: Grossoni
authors.forename: Lucas L
authors.initials: LL
authors.lastname: Colombo
authors.forename: Miriam J
authors.initials: MJ
authors.lastname: Diament
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Kazanietz
authors.forename: Elisa D
authors.initials: ED
authors.lastname: Bal de Kier Joffé
authors.forename: Lydia I
authors.initials: LI
authors.lastname: Puricelli
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Urtreger
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D064593:Heterografts; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D010447:Peptide Hydrolases / Q000378:metabolism; D064546:Protein Kinase C beta / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D025521:Tumor Suppressor Proteins; D051057:Proto-Oncogene Proteins c-akt; D064546:Protein Kinase C beta; D010447:Peptide Hydrolases