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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2006-6-22
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pubmed:abstractText |
Abdominal-type HoxA genes in combination with Meis1 are well-documented on-cogenes in various leukemias but it is unclear how they exert their transforming function. Here we used a system of conditional transformation by an inducible mixed lineage leukemia-eleven-nineteen leukemia (MLL-ENL) oncoprotein to overexpress Hoxa9 and Meis1 in primary hematopoietic cells. Arrays identified c-Myb and a c-Myb target (Gstm1) among the genes with the strongest response to Hoxa9/Meis1. c-Myb overexpression was verified by Northern blot and quantitative reverse transcription-polymerase chain reaction (RT-PCR). Also MLL-ENL activated c-Myb through up-regulation of Hoxa9 and Meis1. Consequently, short-term suppression of c-Myb by small inhibitory RNA (siRNA) efficiently inhibited transformation by MLL-ENL but did not impair transformation by transcription factor E2A-hepatic leukemia factor (E2A-HLF). The anti c-Myb siRNA effect was abrogated by coexpression of a c-Myb derivative with a mutated siRNA target site. The introduction of a dominant-negative c-Myb mutant had a similar but weaker effect on MLL-ENL-mediated transformation. Hematopoietic precursors from mice homozygous for a hypo-morphic c-Myb allele were more severely affected and could be transformed neither by MLL-ENL nor by E2A-HLF. Ectopic expression of c-Myb induced a differentiation block but c-Myb alone was not transforming in a replating assay similar to Hoxa9/Meis1. These results suggest that c-Myb is essential but not sufficient for Hoxa9/Meis1 mediated transformation.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-10082572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-10218098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-10378698,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-10416595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-10521349,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-10698505,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-10757811,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-10996203,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-11113197,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-11687616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-11731795,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-11823037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-11840284,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-12086872,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-12748289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-12800151,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-12941699,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-12941810,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-14525776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-14604967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-14701735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-14962901,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-15674412,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-15755900,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-15774621,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-15867577,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-15919149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-15936140,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-15958703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-16091451,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-16105755,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-16107895,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-16199523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-1709592,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-3380093,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-3498214,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-7527557,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-8563752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-8563753,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-8657149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-8710498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-9315626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16507773-9405651
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
108
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
297-304
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16507773-Animals,
pubmed-meshheading:16507773-Blotting, Northern,
pubmed-meshheading:16507773-Cell Transformation, Neoplastic,
pubmed-meshheading:16507773-Gene Expression Profiling,
pubmed-meshheading:16507773-Gene Expression Regulation, Leukemic,
pubmed-meshheading:16507773-Glutathione Transferase,
pubmed-meshheading:16507773-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:16507773-Hematopoietic Stem Cells,
pubmed-meshheading:16507773-Homeodomain Proteins,
pubmed-meshheading:16507773-Leukemia,
pubmed-meshheading:16507773-Mice,
pubmed-meshheading:16507773-Neoplasm Proteins,
pubmed-meshheading:16507773-Proto-Oncogene Proteins c-myb,
pubmed-meshheading:16507773-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16507773-Up-Regulation
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pubmed:year |
2006
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pubmed:articleTitle |
c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells.
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