Atypical protein kinase C phosphorylates IKKαβ in transformed non-malignant and malignant prostate cell survival

Mechanistic pathways involving atypical protein kinase C-ι (aPKC-ι) have been targeted in various cancer cells such as lung cancer, brain and prostate due to PKCι’s antiapoptotic function, and role in cell proliferation and cell survival. In the current study, we examined the involvement of PKC-ι in the NF-κB pathway following treatment of prostate cells with the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Results demonstrated that androgen-independent DU-145 prostate carcinoma is insensitive to TNFα while transformed non-tumorigenic prostate RWPE-1 cells showed a slight sensitivity to TNFα. However, androgen-dependent LNCaP prostate cells are more sensitive to TNFα treatment and undergo apoptosis. Results demonstrated that in DU-145 cells, TNFα-induced PKC-ι in phosphorylation of IKKαβ. In RWPE-1 cells, PKC-ζ phosphorylates IKKαβ. Degradation of IκBα was observed in all three cell lines, allowing NF-κB/p65 translocation to the nucleus. Although, IKKα is weakly activated in LNCaP cells, the upstream kinase phosphorylation of IKKαβ via aPKCs was not observed. Hence, aPKCs may play a role in activation of NFκB pathway in prostate cancer cells.