Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action

Corinne, Bresson; Keime, Céline; Fauré, Christine; Yann, Letrillard; Maud, Barbado; Sandra, Sanfilippo; Benhra, Najate; Gandrillon, Olivier; Gonin-Giraud, Sandrine

doi:10.1186/1471-2164-8-390

Cited by 14 publications

(19 citation statements)

References 52 publications

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“…The variability observed here is well known in our cell model and it was highlighted in other publications from our laboratory. 13 We suspect it might very well be related to the known stochasticity in gene expression, 18 reinforced by T2ECs being primary cells, stemming from different bone marrow extractions.…”

Section: Introductionmentioning

confidence: 98%

“…10 Hence, v-erbA was thought to act as a negative-dominant mutant of thyroid hormone triiodothyronine and retinoic acid receptor, 11,12 although we have recently demonstrated that the majority of v-erbA target genes were neither T3 nor retinoic acid-target genes. 13 Moreover, the subcellular localization of v-erbA is different from that of c-erbAa1, which also confers on v-erbA other mechanisms of action. 13,14 Our previous works demonstrated that some of these mechanisms were related to the alteration of the mTOR and TGF-b signal transduction pathways in erythroid progenitors.…”

Section: Introductionmentioning

confidence: 99%

“…13 Moreover, the subcellular localization of v-erbA is different from that of c-erbAa1, which also confers on v-erbA other mechanisms of action. 13,14 Our previous works demonstrated that some of these mechanisms were related to the alteration of the mTOR and TGF-b signal transduction pathways in erythroid progenitors. 15 In a previous study, transcriptomes of T2EC expressing either v-erbA or a non-transforming point mutant form of v-erbA, named S61G, were compared using serial analysis of gene expression (SAGE) and RT-qPCR (reverse transcription-quantitative polymerase chain reaction).…”

Section: Introductionmentioning

confidence: 99%

“…15 In a previous study, transcriptomes of T2EC expressing either v-erbA or a non-transforming point mutant form of v-erbA, named S61G, were compared using serial analysis of gene expression (SAGE) and RT-qPCR (reverse transcription-quantitative polymerase chain reaction). 13 Among the genes whose expression varies under the influence of v-erbA, several encode proteins implicated in translation, such as ribosomal proteins S3, S3a, S9, L13; translation initiation factors eIF4A, eIF5, eIF3 and EIF2B2-b; and the elongation factor eEF1-a1. Interestingly, only some, but not all, mRNA-encoding ribosomal proteins are expressed in decreased amounts in v-erbA-expressing cells.…”

Section: Introductionmentioning

confidence: 99%

“…13 To ensure that the total amount of ribosomes was not affected, the quantity of purified ribosomes from v-erbA-or S61G-expressing cells was determined by measuring the absorbance at 260 nm. 16 Statistical analyses of data obtained from 18 independent experiments show no difference between the two cellular conditions (P-value: 0.6429) (Supplementary Data 1).…”

Section: Introductionmentioning

confidence: 99%

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V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors

Nguyen-Lefebvre¹,

Leprun²,

Morin³

et al. 2013

Oncogene

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The v-erbA oncogene transforms chicken erythrocytic progenitors (T2EC) by blocking their differentiation and freezing them in a state of self-renewal. Transcriptomes of T2EC, expressing either v-erbA or a non-transforming form of v-erbA (S61G), were compared using serial analysis of gene expression and some, but not all, mRNA-encoding ribosomal proteins were seen to be affected by v-erbA. These results suggest that this oncogene could modulate the composition of ribosomes. In the present study, we demonstrate, using two-dimensional difference in gel electrophoresis, that v-erbA-expressing cells have a lower amount of RPL11 associated with the ribosomes. The presence of ribosomes devoid of RPL11 in v-erbA-expressing cells was further confirmed by immunoprecipitation. In order to assess the possible impact of these specialized ribosomes on the translational activity, we analyzed proteomes of either v-erbA or S61G-expressing cells using 2D/mass spectrometry, and identified nine proteins present in differing amounts within these cells. Among these proteins, we focused on HSP70 because of its involvement in erythroid differentiation. Our results indicate that, in v-erbA-expressing cells, hsp70 is not only transcribed but also translated more efficiently, as shown by polyribosome fractionation experiments. We demonstrate here, for the first time, the existence of ribosomes with different protein components, notably ribosomes devoid of RPL11, and a regulation of mRNA translation depending on v-erbA oncogene expression.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors

Nguyen-Lefebvre¹,

Leprun²,

Morin³

et al. 2013

Oncogene

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Using a Solver Over the String Pattern Domain to Analyze Gene Promoter Sequences

Rigotti

Mitasiunaite

Besson

et al. 2010

Inductive Databases and Constraint-Based Data Mining

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The effect of oncoprotein v-erbA on thyroid hormone-regulated genes in hepatocytes and their potential role in hepatocellular carcinoma

et al. 2010

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Mutant forms of thyroid hormone receptor (TR) with dominant negative activity are frequently found in human hepatocellular carcinoma (HCC). Interestingly, the v-erbA oncogene, known to exert a dominant-negative effect on the expression of thyroid hormone (T3)-responsive genes, led to the development of HCC in a transgenic mouse model. Thus it is possible that the oncogenic activity of v-erbA in hepatocytes may be mediated by its dominant negative activity on T3-responsive genes. Microarray analysis was used to identify genes differentially expressed in murine hepatocytes in culture (AML12 cells) stably transfected with v-erbA and exposed to T3. The Affymetrix GeneChip Mouse Genome 430 2.0 array consisted of over 39,000 transcripts representing well-known genes. We have identified twenty T3-responsive genes that are negatively regulated by v-erbA at 3 h, and eighteen genes at 24 h, such as follistatin, activin βC, thrombomodulin, Six1, Rasgrp3 and Ndrg2, as well as genes that are regulated by v-erbA only, such as angiopoietin 1 and Igfr2. We have identified T3 responsive genes that are dysregulated by v-erbA. These genes are known to be involved in carcinogenesis. Our studies may provide insight into the potential role of mutant forms of TR in the pathogenesis of HCC.

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Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action

Cited by 14 publications

References 52 publications

V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors

V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors

Using a Solver Over the String Pattern Domain to Analyze Gene Promoter Sequences

The effect of oncoprotein v-erbA on thyroid hormone-regulated genes in hepatocytes and their potential role in hepatocellular carcinoma

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