Artículo
PKC delta (PKCδ) promotes tumoral progression of human ductal pancreatic cancer
Mauro, Laura Valeria
; Grossoni, Valeria C.; Urtreger, Alejandro Jorge
; Yang, Chengfen; Colombo, Lucas Luis
; Morandi, Ana; Pallota, María G.; Kazanietz, Marcelo G.; Bal, Elisa Dora
; Puricelli, Lydia Ines
Fecha de publicación:
01/2010
Editorial:
Lippincott Williams
Revista:
Pancreas
ISSN:
0885-3177
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
OBJECTIVE: Our objective was to study the role of protein kinase C delta (PKCdelta) 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 PKCdelta overexpression on in vivo and in vitro properties of human ductal carcinoma cell line PANC1. RESULTS: Human ductal carcinomas showed PKCdelta overexpression compared with normal counterparts. In addition, in vitro PKCdelta-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 PKCdelta-PANC1. Interestingly, PKCdelta-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 PKCdelta-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 PKCdelta-PANC1 cells developed lung metastasis. CONCLUSION: Our results showed that the overexpression of PKCdelta 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.
Palabras clave:
Human Pancreatic Adenocarcinoma
,
Pkcδ
,
Invasion
,
Pi3k/Akt
,
Erk
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Identificadores
Colecciones
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Mauro, Laura Valeria; Grossoni, Valeria C.; Urtreger, Alejandro Jorge; Yang, Chengfen; Colombo, Lucas Luis; et al.; PKC delta (PKCδ) promotes tumoral progression of human ductal pancreatic cancer; Lippincott Williams; Pancreas; 39; 1; 1-2010; e31-41
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