Induction of expression of growth-related genes by FGF-4 in mouse fibroblasts.
Cells monitor and respond to extracellular signals from polypeptide growth factors by the induction of a genetic program. Although poorly understood at the molecular level, the biological activity of growth factors is believed to be mediated by the regulation of specific sets of genes. We have isolated a number of cDNAs, the expression of whose corresponding RNAs is induced by FGF-4 (K-FGF) in murine NIH3T3 fibroblasts. The cDNAs (FIN, for FGF-inducible) were isolated using a strategy of subtractive hybridization designed to yield 'late' genes which compared transformed 3T3 cells that constitutively produce FGF-4 with their normal counterpart. The 21 independent cDNAs isolated were found to correspond to known genes (FIN1-12), or novel genes (FIN13-21). Expression of the FIN genes is induced in response to FGF-4 as well as to serum in NIH3T3 cells with delayed kinetics, with maximum stimulation occurring 12-18h after growth factor treatment. Induction requires protein synthesis and is mostly transcriptional. FIN1-12 encode a broad range of previously described genes, some of which are proposed to have an important role in cell proliferation. The novel clones include a putative serine-threonine phosphatase (FIN13) and a gene with homology to NTP-binding proteins (FIN16). The distribution of expression of the novel FIN clones in adult mouse tissues was highly restricted, although most were expressed in embryos. While expression of novel FIN cDNAs was strongly regulated in NIH3T3 cells, induction of differentiation in PC-12 cells by FGF-4 (as well as by NGF) did not result in significant induction of expression, suggesting that most of the FIN genes are proliferation-specific. Chromosomal localization of novel FIN clones indicated that each segregated independently to separate mouse chromosomes.
Guthridge
M A
MA
Department of Microbiology and Kaplan Cancer Center, NYU School of Medicine, New York 10016, USA.
Seldin
M
M
Basilico
C
C
D016475:3T3 Cells / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002461:Cell Line, Transformed; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D006133:Growth Substances / Q000235:genetics* / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000494:pharmacology; D051381:Rats; D014018:Tissue Distribution
D018076:DNA, Complementary; C496446:Fgf4 protein, mouse; C496447:Fgf4 protein, rat; D051519:Fibroblast Growth Factor 4; D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors