INVESTIGADORES
URTREGER Alejandro Jorge
congresos y reuniones científicas
Título:
PKC delta promotes a more aggressive tumorigenic phenotype in the human pancreatic carcinoma cell line panc1
Autor/es:
LAURA V. MAURO; VALERIA C. GROSSONI; LUCAS L. COLOMBO; ALEJANDRO J. URTREGER; MARCELO G. KAZANIETZ; CHENFENG YANG; ELISA D. BAL DE KIER JOFFÉ; LYDIA I. PURICELLI
Lugar:
Los Angeles, EEUU.
Reunión:
Congreso; 98th Annual Meeting of the American Associaton for Cancer Research; 2007
Institución organizadora:
American Associaton for Cancer Research (AACR)
Resumen:
The novel delta isoform of the Protein Kinase C (PKCd) plays a critical role in cancer and participates in a variety of signal transduction pathways such as apoptosis and cell proliferation. Its role in the pathogenesis of the pancreatic carcinoma, characterized by a poor prognosis and the resistance to conventional therapy, is almost unknown. The human ductal carcinoma cell line PANC1 expresses PKCd at very low levels, detectable by Western blot analysis. Previously we reported the successful obtention of the cell line PANC1-PKCd, able to overexpress the delta isoform of PKC with functional enzymatic ability. The aim of this work was to study the effect of the stable overexpression of PKCd on in vivo and in vitro properties associated with the tumor progression of PANC1 cell line. PANC1-PKCd results were compared with those obtained with PANC1 cells transfected with the empty vector (PANC1-pMTH). PANC1-PKCd and PANC1-pMTH cells were sc inoculated in nude mice (6 x 106 cells/0.2ml/mouse, n=20). The overexpression of PKCd induced an increase in tumorigenicity of PANC1 cells (Tumor take 83.3 % vs 50.0 % in control cells). Besides, PANC1-PKCd tumors showed a significantly lower latency and a higher growth rate respect to PANC1-pMTH tumors (4.96±1.8 vs 1.34±0,8 mm3/day, p<0.05). PANC1-PKCd tumors showed a marked increase in the number of cycling cells evaluated by immunohistochemistry against Ki-67 antigen and by counting the number of mitotic figures. The in vivo results could be associated with the higher ability of PANC1-PKCd cells to grow in soft agar (11.7±1.2 colonies per 24-multiwell plates vs pMTH: 8.0±1.0, p<0.01). Besides, PANC1-PKCd cells were about 4-fold more resistant to serum starvation and to the treatment with cytotoxic drugs, suggesting that PKCd was able to promote cellular survival and drug resistance in PANC1 cells.In conclusion, our results indicate that the overexpression of PKCd induce a more malignant phenotype in human ductal pancreatic carcinoma cells. Probably the enhancement in clonogenicity and the resistance to stress conditions could be, at least in part, responsible for the observed in vivo effect induced by the novel PKC isoenzyme.