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Identification of a PDGF-responsive element in the murine c-myc gene
1Massachusetts Institute of Technology, Center for Cancer Research, Cambridge 02139.
Abstract:
The c-myc gene is rapidly induced in quiescent Balb/c-3T3 cells in response to the platelet-derived growth factor (PDGF). In order to study the mechanisms by which growth factors regulate induction of c-myc, we have attempted to identify growth factor-responsive elements in the murine c-myc locus. Various fragments of the c-myc gene linked to a bacterial CAT reporter gene were stably transfected into Balb/c-3T3 cells. A construct which includes the P1 promoter and 424 bp of upstream sequences shows a 3-5 fold induction of CAT RNA expression in response to sis/PDGF. S1 nuclease mapping experiments demonstrate that this mRNA initiates from the myc P1 promoter. Nuclear runoff transcription experiments performed with this myc/CAT construct show that this induction occurs at the transcriptional level. Deletion analysis led to the identification of an 81 bp segment in the first exon between the c-myc P1 and P2 promoters which is necessary to confer growth factor responsiveness in this construct.
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