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Published on: December 27, 2016
A novel early growth response gene rapidly induced by fibroblast, epithelial cell and lymphocyte mitogens
V P Sukhatme1, S Kartha, F G Toback
1Department of Human Genetics, Howard Hughes Medical Institute, Philadelphia, Pennsylvania.
Abstract:
Mitogens evoke many alterations in gene expression in eukaryotic cells. Genes which are activated rapidly and transiently, that are evolutionarily conserved and whose induction is shared by diverse cell types when exposed to different growth stimuli are likely to be of critical importance in transducing mitogenic signals and regulating cellular proliferation. c-myc and c-fos are the only known genes fulfilling these criteria. We report on the molecular cloning of a novel early growth response (egr) gene which also satisfies these conditions. In response to serum, its 3.7 kb mRNA is induced dramatically in mouse fibroblasts reaching a peak level at about 30 minutes that is ten times higher than the maximal value attained by c-fos mRNA. This transcript is induced by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate and is "superinduced" by serum and cycloheximide together. Importantly, the gene is highly induced by different mitogens in a wide array of cell types: insulin stimulated rat hepatoma cells, adenosine diphosphate treated monkey kidney epithelial cells, and phytohemagglutinin stimulated human peripheral blood lymphocytes. Given the many properties that this gene shares with c-myc and c-fos, it may play a key role in the control of cell growth and perhaps in oncogenesis.
Insights
Researchers identified a novel early growth response (egr) gene crucial for cell proliferation. This gene, like c-myc and c-fos, is rapidly induced by mitogens across various cell types, suggesting a key role in cell growth and oncogenesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Mitogens induce significant gene expression changes in eukaryotic cells.
- Rapidly activated, conserved genes are vital for signal transduction and cell proliferation.
- c-myc and c-fos are known key regulators of cell growth.
Purpose of the Study:
- To report the molecular cloning of a novel early growth response (egr) gene.
- To characterize the induction patterns and cell-type specificity of this new egr gene.
- To investigate the potential role of this egr gene in cell growth control and oncogenesis.
Main Methods:
- Molecular cloning of a novel egr gene.
- Analysis of mRNA induction in mouse fibroblasts using serum and 12-O-tetradecanoyl-phorbol-13-acetate.
- Assessment of gene induction in various cell types (rat hepatoma, monkey kidney epithelial, human lymphocytes) stimulated by different mitogens.
Main Results:
- A novel egr gene with a 3.7 kb mRNA transcript was cloned.
- Serum dramatically induced the egr mRNA in mouse fibroblasts, peaking at 30 minutes and exceeding c-fos mRNA levels.
- The egr gene was highly induced by various mitogens in diverse cell types, including insulin, ADP, and phytohemagglutinin.
- Co-treatment with serum and cycloheximide "superinduced" the egr transcript.
Conclusions:
- The novel egr gene shares critical properties with c-myc and c-fos.
- This egr gene is a significant early response gene to mitogenic stimuli.
- It likely plays a key role in regulating cellular proliferation and may be involved in oncogenesis.
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