URTREGER Alejandro Jorge
Protein kinase Cd enhances proliferation and survival of murine mammary cells
VALERIA C. GROSSONI; KARINA B. FALBO; MARCELO G. KAZANIETZ; ELISA D. BAL DE KIER JOFFE; ALEJANDRO J. URTREGER
Lugar: New York; Año: 2007 vol. 46 p. 381 - 390
Protein kinase C (PKC) d, a member of the novel family of PKC serine-threonine kinases, has been implicated in negative regulation of proliferation and apoptosis in a large number of cell types, including breast cancer cell lines, and postulated as a tumor suppressor gene. In this study we show that in murine NMuMG mammary cells PKCd promotes a mitogenic response. Overexpression of PKCd in NMuMG cells leads to a significant increase in [3H]-tymidine incorporation and cell proliferation, as well as enhanced ERK-MAPK activation. Activation of PKCd with a phorbol ester leads to elevated cyclin D1 expression and an hyperphosphorylated Rb state. Surprisingly, ectopic expression of PKCd conferred anchorage-independent growth capacity to NMuMG cells. PKCd overexpressors showed enhanced resistant to apoptotic stimuli, such as serum deprivation or doxorubicin treatment, an effect that correlates with hyperactivation of the Akt survival pathway. Our results provide evidence for a role of PKCd as a positive modulator of proliferative and survival signals in immortalized mammary cells. The fact that PKCd exerts differential responses depending on the cell context not only highlights the necessity to carefully understand the signaling events controlled by this PKC in each cell type but also suggests that we should be cautious in considering this kinase a target for cancer therapy.