title: PKC Delta (PKCdelta) promotes tumoral progression of human ductal pancreatic cancer.
abstract: OBJECTIVE
  Our objective was to study the role of protein kinase C delta (PKCdelta) in the progression of human pancreatic carcinoma.
  
  
  METHODS
  Protein kinase C delta expression in human ductal carcinoma (n = 22) was studied by immunohistochemistry. We analyzed the effect of PKCdelta overexpression on in vivo and in vitro properties of human ductal carcinoma cell line PANC1.
  
  
  RESULTS
  Human ductal carcinomas showed PKCdelta overexpression compared with normal counterparts. In addition, in vitro PKCdelta-PANC1 cells showed increased anchorage-independent growth and higher resistance to serum starvation and to treatment with cytotoxic drugs. Using pharmacological inhibitors, we determined that phosphatidylinositol-3-kinase and extracellular receptor kinase pathways were involved in the proliferation of PKCdelta-PANC1. Interestingly, PKCdelta-PANC1 cells showed a less in vitro invasive ability and an impairment in their ability to migrate and to secrete the proteolytic enzyme matrix metalloproteinase-2. In vivo experiments indicated that PKCdelta-PANC1 cells were more tumorigenic, as they developed tumors with a significantly lower latency and a higher growth rate with respect to the tumors generated with control cells. Besides, only PKCdelta-PANC1 cells developed lung metastasis.
  
  
  CONCLUSIONS
  Our results showed that the overexpression of PKCdelta in PANC1 cells induced a more malignant phenotype in vivo, probably through the modulation of cell proliferation and survival, involving phosphatidylinositol-3-kinase and extracellular receptor kinase signaling pathways.
authors.affiliation: Research Area, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Laura V
authors.initials: LV
authors.lastname: Mauro
authors.forename: Valeria C
authors.initials: VC
authors.lastname: Grossoni
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Urtreger
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Yang
authors.forename: Lucas L
authors.initials: LL
authors.lastname: Colombo
authors.forename: Ana
authors.initials: A
authors.lastname: Morandi
authors.forename: María G
authors.initials: MG
authors.lastname: Pallotta
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 L
authors.initials: LL
authors.lastname: Puricelli
mesh_terms: D000368:Aged; D000818:Animals; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D008297:Male; D051379:Mice; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014183:Transplantation, Heterologous
chemical_list: D016895:Culture Media, Serum-Free; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051745:Protein Kinase C-delta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3