Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-10-12
pubmed:abstractText
Aberrant Wnt signaling mediated by mutations affecting APC (adenomatous polyposis coli) or beta-catenin initiates the majority of human colorectal cancers (CRC) and drives tumorigenesis through the activation of specific genes such as MYC. We report here a novel association whereby another oncogenic transcription factor, MYB/c-Myb, is necessary for intestinal adenoma development directed by activated Wnt signaling. APC(Min/+) mice in which c-myb is haploinsufficient survive longer than wild-type APC(Min/+) animals due to a delay in adenoma formation. Intestinal adenomas from APC(Min/+) mice were assessed and found to have high levels of c-myc gene expression. We explored the relationship between activated Wnt signaling and MYB in regulating MYC and found activated beta-catenin in combination with MYB induces robust upregulation of MYC promoter activity, as well as endogenous MYC mRNA and protein expression, in human cells. This cooperation occurred through independent binding of MYB and beta-catenin to the MYC promoter. These data highlight a cooperative function for MYB in the context of activated Wnt signaling and provide a molecular basis for the expression of MYC in CRC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1476-5403
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1530-8
pubmed:meshHeading
pubmed-meshheading:19609274-Adenoma, pubmed-meshheading:19609274-Adenomatous Polyposis Coli, pubmed-meshheading:19609274-Alleles, pubmed-meshheading:19609274-Animals, pubmed-meshheading:19609274-Cell Line, pubmed-meshheading:19609274-Colorectal Neoplasms, pubmed-meshheading:19609274-Humans, pubmed-meshheading:19609274-Mice, pubmed-meshheading:19609274-Mice, Inbred C57BL, pubmed-meshheading:19609274-Mice, Knockout, pubmed-meshheading:19609274-Proto-Oncogene Proteins c-myb, pubmed-meshheading:19609274-Proto-Oncogene Proteins c-myc, pubmed-meshheading:19609274-RNA, Messenger, pubmed-meshheading:19609274-RNA, Small Interfering, pubmed-meshheading:19609274-RNA Interference, pubmed-meshheading:19609274-Signal Transduction, pubmed-meshheading:19609274-Up-Regulation, pubmed-meshheading:19609274-Wnt Proteins, pubmed-meshheading:19609274-beta Catenin
pubmed:year
2009
pubmed:articleTitle
Intestinal adenoma formation and MYC activation are regulated by cooperation between MYB and Wnt signaling.
pubmed:affiliation
Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't