MOLECULAR-CLONING AND FUNCTIONAL-CHARACTERIZATION OF THE HUMAN PLATELET-DERIVED GROWTH-FACTOR-ALPHA RECEPTOR GENE PROMOTER

Expression of the platelet-derived growth factor alpha receptor (PDGF alpha R) is strictly regulated during mammalian development and tumori genesis. The molecular mechanisms involved in the specific regulation of PDGF alpha R expression are unknown, but transcriptional regulation of the PDGF alpha R gene is most likely to be involved, This study de scribes the molecular cloning of the non-coding exon 1 and approximate ly 2 kb of 5' flanking region of the human PDGF alpha R gene, This 5' flanking region is a functional promoter of the PDGF alpha R gene as c oncluded from its capacity to drive luciferase reporter gene expressio n in an orientation dependent way, Analysis of 5' promoter deletion mu tants revealed that the region from -441 to +118, relative to the tran scription initiation site, is sufficient to establish high level promo ter activity, In addition, the morphogen retinoic acid, alone or in co mbination with dibutyryl cAMP, gives a 22-fold induction of PDGF alpha R gene promoter activity in human teratocarcinoma cells, This effect is mediated through specific transcription factor binding within the - 52/+118 region of the PDGF alpha R gene.