Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action
Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action
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DOI：
10.1186/1471-2164-8-390
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发表时间：
2007-10-26
期刊：
影响因子：
4.4
通讯作者：
Gonin-Giraud, Sandrine
中科院分区：
文献类型：
--
作者：
Bresson, Corinne;Keime, Celine;Gonin-Giraud, Sandrine
背景：禽红母细胞增多症病毒携带的v-erba癌基因来源于编码三碘甲状腺原氨酸(T3R)核受体的c-erbaα原癌基因。V-Erba在体外通过阻断红系祖细胞的分化来转化红系祖细胞，推测是通过干扰T3R和RAR(维甲酸受体)。结果：通过基因表达序列分析(SAGE)，我们筛选到了110个与v-Erba基因转化相关的基因。启动子序列的生物信息学分析和转录分析指出了c-Myb在v-erba效应中的潜在作用。此外，根据功能对新发现的靶基因进行分组，揭示了预期的(染色质/转录)和意想不到的(蛋白质代谢)功能，这些功能可能被v-erba解除调控。然后，我们集中研究了15个新的v-erba靶基因，并通过实时定量PCR证明，它们的大部分表达既不被T3激活，也不被RA激活，也不在分化过程中激活。基于已知的v-erba的作用，这是意想不到的。结论：本研究提示v-erba参与了大量新的未预料到的作用机制。
Background: The v-erbA oncogene, carried by the Avian Erythroblastosis Virus, derives from the c-erbA alpha proto-oncogene that encodes the nuclear receptor for triiodothyronine (T3R). v-ErbA transforms erythroid progenitors in vitro by blocking their differentiation, supposedly by interference with T3R and RAR (Retinoic Acid Receptor). However, v-ErbA target genes involved in its transforming activity still remain to be identified.Results: By using Serial Analysis of Gene Expression (SAGE), we identified 110 genes deregulated by v-ErbA and potentially implicated in the transformation process. Bioinformatic analysis of promoter sequence and transcriptional assays point out a potential role of c-Myb in the v-ErbA effect. Furthermore, grouping of newly identified target genes by function revealed both expected (chromatin/ transcription) and unexpected (protein metabolism) functions potentially deregulated by v-ErbA. We then focused our study on 15 of the new v-ErbA target genes and demonstrated by real time PCR that in majority their expression was activated neither by T3, nor RA, nor during differentiation. This was unexpected based upon the previously known role of v-ErbA.Conclusion: This paper suggests the involvement of a wealth of new unanticipated mechanisms of v-ErbA action.