URTREGER Alejandro Jorge
PKC delta (PKCd) promotes tumoral progression of human ductal pancreatic cancer
LAURA V. MAURO; VALERIA C. GROSSONI; ALEJANDRO J. URTREGER; CHENGFEN YANG; LUCAS L. COLOMBO; ANA MORANDI; MARÍA G. PALLOTA; MARCELO G. KAZANIETZ; ELISA D. BAL DE KIER JOFFÉ; LYDIA I. PURICELLI
Wolters Kluwer Health / Lippincott Williams & Wilkins
Lugar: Hagerstown; Año: 2010 vol. 39 p. 31 - 41
Objective: Our objective was to study the role of protein kinase C delta (PKCd) 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 PKCd overexpression on in vivo and in vitro properties of human ductal carcinoma cell line PANC1. Results: Human ductal carcinomas showed PKCd overexpression compared with normal counterparts. In addition, in vitro PKCd-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 PKCd-PANC1. Interestingly, PKCd-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 PKCd-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 PKCd-PANC1 cells developed lung metastasis. Conclusion: Our results showed that the overexpression of PKCd 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.