Characterization of the immediate-early growth response in regenerating liver and insulin-stimulated Reuber H-35 cells

Kenneth L Mohn, University of Pennsylvania


The liver is unique among quiescent, terminally differentiated tissues in its ability to resume proliferation in response to cell loss. Immediate-early genes, whose expression increases independent of de novo protein synthesis during the transition from quiescence to proliferation, play important regulatory roles in the growth response. Characterization of the expression of these genes during liver regeneration and comparison of this response with that of serum-stimulated BALB/c 3T3 cells and insulin-stimulated H-35 hepatoma cells should provide insight into the control of cellular proliferation, the cell type specificity of that control and the role of insulin as a growth factor. Through differential screening of cDNA libraries, we have identified 52 immediate-early genes in the two liver cell systems and 40 appear to be novel. Based on Northern and dot blot analysis, two thirds of these genes are expressed in both liver cells and fibroblasts but 1/3 display tissue-specific expression indicating cell type-specific regulation of the proliferative response. Comparison of our sequences with those identified by other investigators reveals that more than 100 immediate-early genes have been identified in 3T3 cells and more than 70 in the liver cells. This response is unusually complex for the first step in a regulatory cascade suggesting that multiple pathways must be activated and that only a few of these pathways are tissue specific. Interestingly, insulin alone induces a similarly complex response in H-35 cell. The transcription factor genes fra-1, fosB and egr-2 are not expressed at detectable levels in liver cells and c-fos is less abundant than in 3T3 cells. Since these proteins function as dimers, alterations in their expression could affect transcription in a cell type-specific manner. IGFBP-1 was identified as an immediate-early gene whose induction is transcriptionally mediated and specific to regenerating liver. This gene product may regulate liver cell growth and glucose metabolism. PEPCK and IGFBP-1 are transcriptionally inactivated by insulin treatment suggesting that insulin may not participate in the early regenerative response.

Subject Area

Molecular biology|Genetics

Recommended Citation

Mohn, Kenneth L, "Characterization of the immediate-early growth response in regenerating liver and insulin-stimulated Reuber H-35 cells" (1991). Dissertations available from ProQuest. AAI9211974.