Coordinated regulation of c-Myc and Max in rat liver development

Sanders, Jennifer; Gruppuso, Philip A.

doi:10.1152/ajpgi.00545.2004

Cited by 8 publications

(10 citation statements)

References 36 publications

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“…As shown in Fig. 4, the pathway analysis identified that MYC promotes FOS expression [20], and FOS in turn promotes the expression of JUN [21], which binds to TGFBR2 to adjust long-term hypoxia effects on cell proliferation and differentiation [22]. Consistent with our chip results, fos, jun, myc, and tgfbr2 were up-regulated at 2-6, 24, 24, and 72 h, respectively.…”

Section: Discussionsupporting

confidence: 84%

Serial Expression Analysis of Liver Regeneration-Related Genes in Rat Regenerating Liver

et al. 2009

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We investigated the gene expression changes in rat hepatic restoration with Rat Genome 230 2.0 chip containing 11,789 known genes and 13,231 unknown genes (taking up 90 percent of rat whole genome) following a 2/3 hepatectomy. The expression profiles and roles of these genes in rat liver regeneration (LR) were assayed using bioinformatics and systems biology method. Among the above genes, 1,004 known genes and 857 unknown genes were found to be associated with rat LR. The numbers of the known genes up-regulated, down-regulated, and up/down-regulated were 622, 443, and 15, respectively; that of the unknown genes were 367, 400, and 14, respectively. Out of the above two groups of genes, the ones up- and down-regulated 20 times or more were 62 and 38, 8, and 14, respectively. Notably, The highest expression level of dehydrogenase/reductase member 7 (DHRS7) was more than 968-fold compared to control, and alpha-1-B glycoprotein (A1BG), the product of gene with the lowest expression abundance, was 58 times lower than control. During rat liver regeneration, 467 up-regulated, 282 down-regulated, 10 up/down-regulated genes, and 1,031 undetected genes in our study interacted with each other and formed a network with a total of 4,014 connectivities. Among them, the genes for the regulation, synthesis, transport, signal transduction, protein modification, and physiological response formed 630, 290, 691, 373, 2010, and 20 connectivities, respectively; and the genes jun, fos, myc, ptgs2, ccna2, ccl2 had relatively higher degree of connectivity. The results indicated that cell apoptosis and inflammatory response were enhanced in the initial phase and the early part of progressive phase in LR.

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Section: Discussionsupporting

confidence: 84%

Serial Expression Analysis of Liver Regeneration-Related Genes in Rat Regenerating Liver

et al. 2009

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“…Using the WB-F344 cells, we examined the effect of mTOR on members of the Myc signaling network using a multiplex RNase protection assay [29]. Results (Figure 2) showed that rapamycin exposure for 6 hr induced a decrease in the steady state expression of Max and Mad 4.…”

Section: Resultsmentioning

confidence: 99%

Regulation of Gene Expression in Hepatic Cells by the Mammalian Target of Rapamycin (mTOR)

et al. 2010

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BackgroundWe investigated mTOR regulation of gene expression by studying rapamycin effect in two hepatic cell lines, the non-tumorigenic WB-F344 cells and the tumorigenic WB311 cells. The latter are resistant to the growth inhibitory effects of rapamycin, thus providing us with an opportunity to study the gene expression effects of rapamycin without confounding effects on cell proliferation.Methodology/Principal FindingsThe hepatic cells were exposed to rapamycin for 24 hr. Microarray analysis on total RNA preparations identified genes that were affected by rapamycin in both cell lines and, therefore, modulated independent of growth arrest. Further studies showed that the promoter regions of these genes included E-box-containing transcription factor binding sites at higher than expected rates. Based on this, we tested the hypothesis that c-Myc is involved in regulation of gene expression by mTOR by comparing genes altered by rapamycin in the hepatic cells and by c-Myc induction in fibroblasts engineered to express c-myc in an inducible manner. Results showed enrichment for c-Myc targets among rapamycin sensitive genes in both hepatic cell lines. However, microarray analyses on wild type and c-myc null fibroblasts showed similar rapamycin effect, with the set of rapamycin-sensitive genes being enriched for c-Myc targets in both cases.Conclusions/SignificanceThere is considerable overlap in the regulation of gene expression by mTOR and c-Myc. However, regulation of gene expression through mTOR is c-Myc-independent and cannot be attributed to the involvement of specific transcription factors regulated by the rapamycin-sensitive mTOR Complex 1.

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“…For example, the expression of Cdc20 and Hells, genes involved in mitosis, are increased in WT but not in E2F2 Ϫ/Ϫ cells. Intriguingly, Myc, an immediate early gene (33), is only upregulated in E2F2 Ϫ/Ϫ mice. It is also interesting to note that WT mice show greater expression of many genes involved in key mitochondrial processes, indicative of higher mitochondrial activities.…”

Section: E2f1mentioning

confidence: 99%

A role for transcription factor E2F2 in hepatocyte proliferation and timely liver regeneration

Delgado

Fresnedo²,

Iglesias

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Present evidence suggests that E2F2 may act both as a suppressor and promoter of proliferation, depending on the cellular context. We used a loss-of-function mutant mouse model to investigate the function of E2F2 in liver regeneration after partial hepatectomy, a paradigm of cell-cycle progression. Liver mass recovery and histology were examined over 9 days in 70% hepatectomized E2F2Ϫ/Ϫ and wild-type animals. Transcriptome analysis was performed in quiescent and 48-h regenerating liver samples. TIGR MultiExperiment Viewer was used for the statistical analysis of microarray data, significance was determined by Fischer, and P values were adjusted applying BenjaminiHochberg multiple-testing correction. We show that E2F2 is required for adult hepatocyte proliferation and for timely liver regeneration, as disruption of the E2F2 gene in hepatocytes leads to a reduced rate of S-phase entry and to delayed liver regeneration. Transcriptome analysis followed by ontological classification of differentially expressed genes and gene-interaction network analysis indicated that the majority of genes involved in normal liver regeneration were related to biosynthetic and catabolic processes of all major biomolecules as well as cellular location and intracellular transport, confirming the complex nature of the regeneration process. Remarkably, transcripts of genes included in functional categories that are crucial for cell cycle, apoptosis and wound-healing response, and fibrosis were absent in the transcriptome of posthepatectomized E2F2 Ϫ/Ϫ mice. Our results indicate that the transcriptional activity of E2F2 contributes to promote adult hepatocyte proliferation and liver regeneration. cell cycle; transcriptome; liver repair; partial hepatectomy THE E2F TRANSCRIPTION FACTORS are key regulators of cell proliferation and rate-limiting factors in the S-phase entry, as they regulate the expression of many genes involved in the G 1 /S transition. According to the most accepted model of cell-cycle control, unphosphorylated retinoblastoma tumor suppressor protein (pRb) binds to E2F in G 0 /G 1 , forming a complex that actively represses E2F-responsive genes. In late G 1 pRb is inactivated because of phosphorylation by cyclin-dependent kinases, releasing free E2Fs that activate the expression of their target genes (4,12,42).The E2F family is presently composed of nine members encoded by eight different genes (E2F1-8) (4,12,20,42).Members of E2F family can be classified into "activators" (E2F1-3a) and "repressors" (E2F3b-8). Activator E2Fs are considered potent activators of transcription and positive regulators of the cell cycle. Overexpression of any of these activator E2Fs is sufficient to promote G 1 /S transition and DNA replication in immortalized, quiescent rodent fibroblasts in the absence of growth factors (23). However, there is increasing evidence that they may also act as transcriptional repressors (2,7,18,28). E2F1 seems to act both as an oncogene and as a tumor suppressor in the liver (6) but was found not to be essential f...

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Coordinated regulation of c-Myc and Max in rat liver development

Cited by 8 publications

References 36 publications

Serial Expression Analysis of Liver Regeneration-Related Genes in Rat Regenerating Liver

Serial Expression Analysis of Liver Regeneration-Related Genes in Rat Regenerating Liver

Regulation of Gene Expression in Hepatic Cells by the Mammalian Target of Rapamycin (mTOR)

A role for transcription factor E2F2 in hepatocyte proliferation and timely liver regeneration

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