Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action.
BACKGROUND
The v-erbA oncogene, carried by the Avian Erythroblastosis Virus, derives from the c-erbAalpha 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.


CONCLUSIONS
This paper suggests the involvement of a wealth of new unanticipated mechanisms of v-ErbA action.
Bresson
Corinne
C
Université de Lyon, Lyon, F-69003, France . bresson@cgmc.univ-lyon1.fr
Keime
Celine
C
Faure
Claudine
C
Letrillard
Yann
Y
Barbado
Maud
M
Sanfilippo
Sandra
S
Benhra
Najate
N
Gandrillon
Olivier
O
Gonin-Giraud
Sandrine
S
D001665:Binding Sites; D020869:Gene Expression Profiling; D018776:Genes, erbA; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism
D020598:Proto-Oncogene Proteins c-myb