URTREGER Alejandro Jorge
congresos y reuniones científicas
Biological effects of PKCd overexpression in a human pancreatic carcinoma cell line (panc1)
VALERIA C. GROSSONI; ALEJANDRO J. URTREGER; LAURA V. MAURO; ELISA D. BAL DE KIER JOFFÉ; LYDIA I. PURICELLI
Congreso; 96th Annual Meeting of the American Association for Cancer Research (AACR); 2005
American Association for Cancer Research (AACR)
Protein kinase C is a multigene family of serine/threonine kinases that are central to many signal transduction pathways, involving cellular growth, transformation and differentiation. The deregulation of these enzymes has been shown to be important in malignant transformation and metastatic disease. However, because of the great variety of isoforms and their differential expression in various tissues, the functional relevance of each PKC isoform is unclear. Pancreatic carcinoma is characterized by poor prognosis and lack of response to conventional therapy. The ethiology of this disease is not completely known. The goal of this work was to assess the effect of the overexpression of PKCd (delta) on proliferation of the human pancreatic cancer cells, PANC-1, and its relationship to in vitro properties associated with tumoral behavior. PKCd overexpression was achieved by stable transfection while control cells were transfected with the empty pMTH expression vector. PKCd overexpression did not modify the growth rate of PANC-1 cells (Population doubling time: 46.9 h and 45.3 h in transfected and control cells respectively). The adittion of PMA (50 nM) induced a decrease in the proliferation rate of both PKCd and control cells. However, this effect was significantly less evident in PKCd cells (57.7 h vs 66.4 h in control cells, p<0.01). PANC-1-PKCd cells showed an increase in the adhesiveness respect to control cells (p<0.05). This effect was not modulated by PMA addition. Besides, we observed that PKCd overexpression induced a decrease in the migratory ability of the pancreatic carcinoma cells, measured by a wound assay; PKCd transfectants migrated 1.8 x 107 ± 5.3 x 106 vs 2.5 x 107± 3.1 x 106 AU (arbitrary units) in control cells (p <0.01), after 48 h. On the other hand, PKCd expressing cells showed a marked reorganization of the actin cytoskeleton with loss of stress fibers. Our results suggest that PKCd transfection induces several changes in the pancreatic tumor cells associated with a less transformed fenotype.