The net outcome of SAG-mediated inhibition of c-Jun/AP-1 (pro-tumor promotion) and of p27 (antiproliferation) increased skin hyperplasia, with no apparent effect on apoptosis, as evidenced by increased skin thickness, and increased rate of DNA synthesis, but hardly any apoptosis.
Activation of activator protein 1 (AP-1) and nuclear factor kappaB (NFkappaB)-dependent transcription is required for tumor promotion in cell culture models and transgenic mice.
Overall, these results indicate that MnSOD regulates both cellular redox status and selectively modulates PKCepsilon signaling, thereby delaying AP-1 activation and inhibiting tumor promotion, resulting in reduction of tumors in MnSOD transgenic mice.
Although the c-jun oncogene is an integral part of the AP-1 transcriptional complex implicated in the process of tumor promotion, its role in the pathogenesis of human tumors is unknown.