Growth Factors Regulate Transin Gene Expression by c-fos--Dependent and c-fos--Independent Pathways

• Published in: Science (American Association for the Advancement of Science) 1988-12, Vol.242 (4884), p.1424-1427
• Main Authors: Kerr, Lawrence D., Holt, Jeffrey T., Matrisian, Lynn M.
• Format: Article
• Language: English
• Subjects: 3T3 cells; Animals; Biochemistry; Biological and medical sciences; Cell growth; Cell lines; Cells; Cells, Cultured; DNA; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Genes - drug effects; Genetic aspects; Genetics; Growth factors; Growth Substances - pharmacology; Humans; Matrix Metalloproteinase 3; Medical research; Metalloendopeptidases - genetics; Metalloenzymes; Mice; Molecular and cellular biology; Molecular genetics; Neoplasm Proteins - genetics; NIH 3T3 cells; Oligomers; Oligonucleotides; Oncogenes; Proto-Oncogenes - drug effects; RNA; RNA - genetics; RNA, Antisense; RNA, Messenger - antagonists & inhibitors; Tetradecanoylphorbol Acetate - pharmacology; Transcription, Genetic - drug effects; Transfection
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2462278

The rapid induction of the proto-oncogene c-fos by growth factors and other bioactive agents, and the recent evidence that the c-fos protein (Fos) is associated with transcriptional complexes, suggests that Fos may represent an integral part of an intracellular messenger pathway that triggers changes in gene expression and ultimately phenotypic alterations. This report examines the role of c-fos in growth factor stimulation of transin, a matrix-degrading secreted metalloproteinase. Platelet-derived growth factor (PDGF) stimulation of transin RNA was blocked by a selective reduction in Fos synthesis with antisense c-fos mRNA, whereas epidermal growth factor (EGF) stimulation of transin occurred despite an equivalent inhibition of Fos levels. The stimulatory effect of both PDGF and EGF on transin transcription involved factors recognizing the sequence TGAGTCA, which is found in the transin promoter and is reported to be a binding site for the transcriptional factor Jun/AP-1 and for associated Fos and Fos-related complexes. Thus both Fos-dependent and Fos-independent pathways exist for growth factor regulation of gene expression, and both effects may be mediated through the same cis-acting transcription element.