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Induction of expression of growth-related genes by FGF-4 in mouse fibroblasts
M A Guthridge1, M Seldin, C Basilico
1Department of Microbiology and Kaplan Cancer Center, NYU School of Medicine, New York 10016, USA.
Abstract:
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.
Insights
Researchers identified FGF-inducible (FIN) genes in mouse cells responding to growth factors. These genes, including novel ones, are primarily involved in cell proliferation and show restricted tissue expression.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Cells respond to extracellular polypeptide growth factors via genetic programs.
- The molecular mechanisms underlying growth factor-mediated gene regulation are not fully understood.
Purpose of the Study:
- To identify and characterize genes induced by Fibroblast Growth Factor-4 (FGF-4) in NIH3T3 fibroblasts.
- To investigate the role of these FGF-inducible (FIN) genes in cellular processes like proliferation and differentiation.
Main Methods:
- Subtractive hybridization was used to isolate FGF-inducible cDNAs (FIN genes).
- Expression patterns of FIN genes were analyzed in NIH3T3 cells and various mouse tissues.
- The study also examined FIN gene expression during differentiation in PC-12 cells.
Main Results:
- Twenty-one independent FIN cDNAs were isolated, including known (FIN1-12) and novel genes (FIN13-21).
- FIN gene expression was induced by FGF-4 and serum in NIH3T3 cells with delayed kinetics, requiring protein synthesis and primarily occurring at the transcriptional level.
- Novel FIN clones included a putative serine-threonine phosphatase (FIN13) and an NTP-binding protein homolog (FIN16).
- Most novel FIN genes showed restricted expression in adult tissues but were present in embryos.
- FIN gene induction was largely specific to proliferation, as differentiation in PC-12 cells did not significantly induce their expression.
- Novel FIN clones were mapped to independent mouse chromosomes.
Conclusions:
- FGF-4 induces a set of 'late' FGF-inducible (FIN) genes in fibroblasts, many of which are novel.
- These FIN genes, particularly the novel ones, appear to be primarily involved in cell proliferation.
- The study provides insights into the genetic response to growth factors and identifies new genes with potential roles in cell growth and development.