A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappa B or ODC transactivation

Pdcd4 is a novel transformation suppressor that is highly expressed in prom otion-resistant (P-) mouse epidermal JB6 cells but not in susceptible (P+) cells. Overexpression of pdcd4 cDNA in stably transfected P+ cells rendered cells resistant to tumor promoter-induced transformation, indicating that elevated expression of Pdcd4 protein is sufficient to suppress neoplastic t ransformation. To determine whether Pdcd4 suppresses neoplastic transformat ion through inhibiting known transformation required events, se examined th e possibility that pdcd4 inhibited the activation of AP-1 or NF-kappaB depe ndent transcription or of ornithine decarboxylase (ODC) activity. Activatio n of AP-1-dependent transcriptional activity mas inhibited bai pdcd4 expres sion in a concentration dependent manner. In contrast, Pdcd4 slightly incre ased NF-kappaB-dependent transcription and did not alter ODC enzymatic acti vity. Previous studies suggested that activation of AP-1 was required for P + cell transformation as well as for tumor promotion in vivo. These results indicate that Pdcd4 functions as a transformation suppressor, possibly thr ough inhibiting AP-1 activation in combination with other factors such as e nhancing NF-kappaB activation. Pdcd4 may thus constitute a useful molecular target for cancer prevention.