PKC-zeta associates and phosphorylates IKK-α/β in breast cancer cells Free

LB-30

Breast cancers are highly lethal tumors and are one of the leading causes of death among women. The objective of this study was to focus on the role of protein kinase C-zeta (PKC-ζ) in breast cancer cell survival through the NF-κB pathway. It has been previously demonstrated that Tumor Necrosis Factor alpha (TNF-α) induces the NF-κB pathway and plays a critical role in the survival and apoptotic pathways. In the present study, we determined whether PKC-ζ associates with the inhibitor of nuclear factor kappa-B kinase-α /β (IKK-α /β) in breast cancer cells. Estrogen independent MDA-MB 468 breast cancer cells were treated with PKC-ζ short interfering RNAs (siRNA) for 24, 48, and 72 hours. The cells were than treated with TNF-α for 20 minutes. Western blots of PKC-ζ in IKK-α /β immunoprecipitates depicted an association of IKK-α /β with PKC-ζ. Additionally, Western blots probing for phosphorylated IKK-α /β demonstrated that cells treated with PKC-ζ siRNA and immunoprecipitated for IKK-α /β had significantly reduced phosphorylated IKK-α /β compared to the control siRNA-A. These results suggest that treatment of MDA-MB-468 breast cancer cells with TNF-α promotes the association of PKC-ζ with IKK-α /β leading to phosporylation and activation of IKK-α /β.