URTREGER Alejandro Jorge
congresos y reuniones científicas
Effect of different PKC isoforms on proliferation, survival and invasiveness in human pancreatic carcinoma cell line (panc1)
VALERIA C. GROSSONI; LAURA V. MAURO; ALEJANDRO J. URTREGER; MARCELO G. KAZANIETZ; ELISA D. BAL DE KIER JOFFÉ; LYDIA I. PURICELLI
Congreso; 97th Annual Meeting of the American Association for Cancer Research; 2006
American Association for Cancer Research (AACR)
PKCs constitute a serin-threonin kinase family that have a key role in malignant transformation. The functional relevance of each PKC isoform is unclear, because of their differential expression in different tissues. Pancreatic carcinoma is characterized by poor prognosis and lack of response to conventional therapy. The ethiology of this disease is almost unknown. The aim of this work was to study the effect of PKC delta (d) and PKC zeta (z) overexpression on in vitro properties associated with the tumoral behavior of the human pancreatic cancer cells, PANC-1. In every case, cells transfected with the empty vectors were used as controls (C). The invasive ability of PANC-1 cells, assessed in matrigel-coated transwell chambers, was inhibited by the overexpression of PKCd and enhanced by PKCz (PKCz: 12.54±1.8 vs C: 6.53±0.8 invasive cells/field, p<0.05; PKCd: 3.01±1.2, vs C: 11.44±3.3 cells/field, p<0.05). In the case of PKCd this behavior was associated with a decrease in MMPs activity, while uPA secretion was not modulated. On the other hand, neither uPA nor MMPs seemed to be involved in the higher invasive ability of PANC-PKCæ cells. While overexpression of PKCz promoted the clonogenic ability of PANC-1 cells, PKCd showed no effect on this property. Finally we demonstrated that neither PANC-d or PANC-PKCz cells differ from control cells in their susceptibility to cytotoxicity induced by doxorrubicin. However, when PANC-PKCd cells were exposed to the phorbol ester PMA, cells became resistant to the cytotoxic treatment. Our results suggest that the overexpression of PKCz induced a more malignant phenotype associated with the enhancement in invasiveness and clonogenicity. On the contrary, PKCd overexpression was associated with a more normal phenotype due to the decrease in the proteolytic secretion and in consequence in invasiveness.