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.

CONCLUSION:

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: Laura V Mauro, Valeria C Grossoni, Alejandro J Urtreger, Chengfeng Yang, Lucas L Colombo, Ana Morandi, María G Pallotta, Marcelo G Kazanietz, Elisa D Bal de Kier Joffé, Lydia L Puricelli
• Journal: Pancreas (Pancreas) Vol. 39 Issue 1 Pg. e31-41 (Jan 2010) ISSN: 1536-4828 [Electronic] United States
• PMID: 19924022 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Serum-Free
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Protein Kinase C-delta
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Aged
• Animals
• Blotting, Western
• Carcinoma, Pancreatic Ductal (enzymology, genetics, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Culture Media, Serum-Free (pharmacology)
• Disease Progression
• Female
• Humans
• Immunohistochemistry
• Lung Neoplasms (enzymology, genetics, secondary)
• Male
• Mice
• Middle Aged
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Neoplasms, Experimental (enzymology, genetics, pathology)
• Pancreatic Neoplasms (enzymology, genetics, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Protein Kinase C-delta (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Transplantation, Heterologous