Identification of a phorbol ester responsive region in the myeloid-specific promoter of the c-fgr proto-oncogene.

Expression of the c-fgr proto-oncogene is activated during differentiation of myeloid cells. We used a luciferase reporter assay to identify sequences that regulate c-fgr gene transcription during differentiation of human U937 promonocytic cells, induced by phorbol 12-myristate 13-acetate (PMA) or by tumour necrosis factor-alpha (TNF-alpha) and 1,25-dihydroxycholecalciferol (1,25-DHCC). We found that the region from nucleotides -344 to -116, with respect to the transcriptional start site, is required for basal activity of the c-fgr promoter in U937 cells, and that the region from nucleotides -1211 to -752 is responsive to PMA. No sequence elements responsive to TNF-alpha and 1,25-DHCC were found, suggesting that these agents induce c-fgr mRNA accumulation by a mechanism differing from that mediating the effects of PMA.