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 tumorigenesis. The molecular mechanisms involved in the specific regulation of PDGF alpha R expression are unknown, but transcriptional regulation of the PDGF alpha R...

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Published inOncogene Vol. 10; no. 8; p. 1667
Main Authors Afink, G B, Nistér, M, Stassen, B H, Joosten, P H, Rademakers, P J, Bongcam-Rudloff, E, Van Zoelen, E J, Mosselman, S
Format Journal Article
LanguageEnglish
Published England 20.04.1995
Subjects
Base Sequence
Bucladesine - pharmacology
Cloning, Molecular
Humans
Molecular Sequence Data
Promoter Regions, Genetic
Receptors, Platelet-Derived Growth Factor - genetics
TATA Box
Theophylline - pharmacology
Tretinoin - pharmacology
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Summary:Expression of the platelet-derived growth factor alpha receptor (PDGF alpha R) is strictly regulated during mammalian development and tumorigenesis. 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 describes the molecular cloning of the non-coding exon 1 and approximately 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 concluded from its capacity to drive luciferase reporter gene expression in an orientation dependent way. Analysis of 5' promoter deletion mutants revealed that the region from -441 to +118, relative to the transcription initiation site, is sufficient to establish high level promoter activity. In addition, the morphogen retinoic acid, alone or in combination 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.
ISSN:0950-9232