Epidermal growth factor and platelet-derived growth factor regulate the activity of the insulin-like growth factor I gene promoter.
The expression of insulin-like growth factor I (IGF-I) is regulated by hormones, oncogenes, and other growth factors, and is markedly decreased or even absent in senescent human diploid fibroblasts. In previous articles, we have reported that the SV40 large T antigen increases the production of IGF-I and that the expression of the IGF-I gene is negatively regulated by an E2F binding site in the IGF-I promoter. We have now investigated the activity of the IGF-I promoter, in response to stimulation of cells by either PDGF or EGF. Both growth factors stimulate the activity of the IGF-I promoter, indicating that they regulate the levels of expression of IGF-I. When the E2F binding sequence in the IGF-I promoter is mutated, the IGF-I promoter is constitutively active and no longer responds to the action of growth factors.
Li
S
S
Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Baserga
R
R
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D051381:Rats; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D010982:Platelet-Derived Growth Factor; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D015500:Chloramphenicol O-Acetyltransferase