PKC Delta (PKCδ) Promotes Tumoral Progression of Human Ductal Pancreatic Cancer

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Abstract
Objective: Our objective was to study the role of protein kinase C delta (PKCδ) 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 PKCδ overexpression on in vivo and in vitro properties of human ductal carcinoma cell line PANC1. Results: Human ductal carcinomas showed PKCδ overexpression compared with normal counterparts. In addition, in vitro PKCδ-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 PKCδ-PANC1. Interestingly, PKCδ-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 PKCδ-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 PKCδ-PANC1 cells developed lung metastasis. Conclusion: Our results showed that the overexpression of PKCδ 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.

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