Protein kinase C delta inhibits the production of proteolytic enzymes in murine mammary cells.


In previous studies we have determined that protein kinase C (PKC) delta, a widely expressed member of the novel PKC serine-threonine kinases, induces in vitro changes associated with the acquisition of a malignant phenotype in NMuMG murine mammary cells. In this study we show that PKCdelta overexpression significantly decreases urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) production, two proteases associated with migratory and invasive capacities. This effect is markedly enhanced by treatment with phorbol 12-myristate 13-acetate (PMA). On the other hand, depletion of PKCdelta using RNAi led to a marked increase in both uPA and MMP-9 secretion, suggesting a physiological role for PKCdelta in controlling protease secretion. The MEK-1 inhibitor PD98059 reverted the characteristic pattern of proteases secretion and phospho-ERK1/2 up-regulation observed in PKCdelta overexpressors, suggesting that the PKCdelta effect is mediated by the MEK/ERK pathway. Our results suggest a dual role for PKCdelta in murine mammary cell cancer progression. While this kinase clearly promotes mitogenesis and favors malignant transformation, it also down-modulates the secretion of proteases probably limiting metastatic dissemination.


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@article{Grossoni2007ProteinKC, title={Protein kinase C delta inhibits the production of proteolytic enzymes in murine mammary cells.}, author={Valeria C. Grossoni and Karina B. Falbo and Laura Valeria Mauro and Martin Alejandro Krasnapolski and Marcelo G Kazanietz and Elisa Dora Bal de Kier Joff{\'e} and Alejandro J. Urtreger}, journal={Clinical & experimental metastasis}, year={2007}, volume={24 7}, pages={513-20} }