Mechanism of regulation of PDGF-A chain gene expression by serum and TPA.

ABSTRACT

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.