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

Mechanistic pathways involving atypical protein kinase C-iota (aPKC-iota) have been targeted in various cancer cells such as lung cancer, brain and prostate due to PKC iota's antiapoptotic function, and role in cell proliferation and cell survival. In the current study, we examined the involvement of PKC-iota in the NF-kappa B pathway following treatment of prostate cells with the pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha). Results demonstrated that androgen-independent DU-145 prostate carcinoma is insensitive to TNF alpha while transformed non-tumorigenic prostate RWPE-1 cells showed a slight sensitivity to TNF alpha. However, androgen-dependent LNCaP prostate cells are more sensitive to TNF alpha treatment and undergo apoptosis. Results demonstrated that in DU-145 cells, TNF alpha-induced PKC-iota in phosphorylation of IKK alpha beta. In RWPE-1 cells, PKC-zeta, phosphorylates IKK alpha beta. Degradation of I kappa B alpha was observed in all three cell lines, allowing NF-kappa B/p65 translocation to the nucleus. Although, IKK alpha is weakly activated in LNCaP cells, the upstream kinase phosphorylation of IKK alpha beta via aPKCs was not observed. Hence, aPKCs may play a role in activation of NF kappa B pathway in prostate cancer cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.