Insulin-like growth factor-I stimulates c-fos and c-jun transcription in PC12 cells.

We analyzed the effects of insulin-like growth factor-I (IGF-I), a polypeptide growth factor which exerts mitogenic effects via specific membrane receptors. The control of IGF-I on c-fos and c-jun transcription was studied in PC12 cells. Gel mobility shift assays with a labeled AP1 consensus binding sequence (TRE: TGACTCA) showed an increase in specific binding upon trIGF-treatment. Gene transfer studies revealed that the increase in AP1 binding is functional since IGF-I stimulates transcription from a reporter gene containing the minimal TRE linked to the chloramphenicol acetyl transferase (CAT) reporter gene. To further characterize the molecular mechanism by which IGF-I increases AP1 activity, we analysed the transcription regulation of c-fos and c-jun using reporter genes containing the respective promoters or specific regulatory elements. Deletion studies with the c-jun promoter, showed that IGF-I stimulates c-jun transcription via a cis acting element(s) localized within the 132 base pairs prior to the transcription start site; possibly the AP1 like element TGACATCA. Similar studies revealed that c-fos stimulation by IGF-I requires the presence of a regulatory sequence spanning the dyad symmetry element (DSE) and the fos AP1-like sequence (FAP). Further experiments using specific elements linked to the minimal unresponsive c-fos promoter, showed that the DSE is the main target for c-fos induction by IGF-I.