EARLY RESPONSES OF SIHA HUMAN SQUAMOUS CARCINOMA-CELLS TO HYPOXIC SIGNALS - EVIDENCE OF PARALLEL ACTIVATION OF NF-KAPPA-B AND AP-1 TRANSCRIPTIONAL COMPLEXES

We compared the responses of c-Jun/AP-1 transcriptional complexes with those of NF-kappa B, an established hypoxia-inducible transcriptional complex, in hypoxic SiHa human squamous carcinoma cells. We observed that NF-kappa B was activated rapidly, while AP-1 activation was detec table only after prolonged hypoxia. However, in parallel with NF-kappa B activation, hypoxia induced a protein kinase activity that could ph osphorylate the transactivation domain of the ATF-2 transcription fact or in vitro. Taken together, these experiments indicate that NF-kappa B can rapidly transduce hypoxic signals through increased DNA-binding and transactivation activities, whereas specific AP-1 (ATF-2/c-Jun) co mplexes may be activated under the same hypoxic conditions by a stress -reponsive MAPK pathway.