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Poster De Conférence Année : 2006

New mechanisms of v-ErbA oncogene action revealed by SAGE analysis

Résumé

The v-erbA oncogene, carried by the Avian Erythroblastosis Virus, derives from the c-erbAalpha proto-oncogene which encodes the nuclear receptor for the thyroid hormone triiodothyronine (T3). In vitro, v-ErbA transforms erythroid progenitors by blocking their differentiation. It has been proposed that v-ErbA acts as a transcriptional repressor for genes normally activated by T3 and retinoic acid (RA), upregulated during the differentiation process. However, v-ErbA target genes responsible for transformation have yet to be identified. We used Serial Analysis of Gene Expression (SAGE) to analyze the transcriptome of avian erythroid progenitors (T2ECs), the natural target cells of v-erbA, expressing either an oncogenic form or a non-transforming form of verbA. The comparison of these two libraries revealed 83 genes differentially expressed between these two conditions. So far, the differential expression for 16 of them has been confirmed by real-time PCR on multiple independent repetitions. We observed that, among these v-ErbA target genes, some are activated by T3 and RA. This confirms that activation by T3 and RA receptors is indeed inhibited by v-ErbA. However, the expression of a vast majority of v-ErbA target genes did not vary in response to T3 and RA. These results suggest that v-ErbA must also act by T3- and RA-independent mechanisms in the transformation process. Furthermore, most v-erbA target genes do not vary during the differentiation process, in contrast to the expected role of v-erbA. In order to determine which major functions are deregulated by v-ErbA, we clustered the target genes identified according to the cellular function encoded by their corresponding proteins. We found that many of them are involved in the protein translation process. In order to understand the molecular mechanisms responsible for the coordinated variation of the v-ErbA target gene, we analyzed their promoter sequences and found the presence of c-myb binding sites as a signature motif of v-erbA target genes. This suggests a role for c-myb in the v-erbA-induced transformation process. Altogether, these studies demonstrate the involvement of new mechanisms pointing toward an unanticipated complexity of v-erbA oncogene action.
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Dates et versions

hal-01613844 , version 1 (10-10-2017)

Identifiants

  • HAL Id : hal-01613844 , version 1

Citer

Corrine Bresson, Céline Keime, Claudine Faure, Yann Letrillard, Ieva Mitasiunaite, et al.. New mechanisms of v-ErbA oncogene action revealed by SAGE analysis. Integrative Post-Genomics, IPG'06, Nov 2006, Lyon, France. 2006. ⟨hal-01613844⟩
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