Mechanism of regulation of PDGF-A chain gene expression by serum and TPA.
The state of induction of the platelet-derived growth factor (PDGF) A chain markedly differs among drugs and cells. The increase in A chain mRNA by serum was due to activation of transcription. Transcription was also activated by cycloheximide (CHX) even during serum starvation, indicating that the expression of the PDGF-A chain is inhibited by transcription suppressor factor with a short life during serum starvation. On the other hand, post-transcriptional regulation played a very important role in the increase in A chain mRNA by 12-O-tetradecanoylphorbol-13-acetate (TPA) and superinduction by TPA and CHX. We also analyzed the regions of PDGF-A chain gene that respond to serum and TPA by the chloramphenicol acetyltransferase (CAT) assay and the gel retardation assay. The region from TATA to -135 bp has the activity of the basal expression of PDGF-A chain gene and is considered to be involved in down regulation after the treatment with serum and TPA. Elements that respond to serum and increase the expression of PDGF-A chain gene are present in the region from -135 bp to -223 bp. Elements that inhibit the expression of PDGF-A chain gene during serum starvation are present in the region from -223 bp to -416 bp.
Department of Internal Medicine, Hiroshima University, Japan.
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Takimoto
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Kuramoto
D001483:Base Sequence; D001769:Blood; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate