Linked Life Data

18593912

Source:http://linkedlifedata.com/resource/pubmed/id/18593912

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2008-7-2
pubmed:abstractText
MYC overexpression has been implicated in the pathogenesis of most types of human cancers. MYC is likely to contribute to tumorigenesis by its effects on global gene expression. Previously, we have shown that the loss of MYC overexpression is sufficient to reverse tumorigenesis. Here, we show that there is a precise threshold level of MYC expression required for maintaining the tumor phenotype, whereupon there is a switch from a gene expression program of proliferation to a state of proliferative arrest and apoptosis. Oligonucleotide microarray analysis and quantitative PCR were used to identify changes in expression in 3,921 genes, of which 2,348 were down-regulated and 1,573 were up-regulated. Critical changes in gene expression occurred at or near the MYC threshold, including genes implicated in the regulation of the G(1)-S and G(2)-M cell cycle checkpoints and death receptor/apoptosis signaling. Using two-dimensional protein analysis followed by mass spectrometry, phospho-flow fluorescence-activated cell sorting, and antibody arrays, we also identified changes at the protein level that contributed to MYC-dependent tumor regression. Proteins involved in mRNA translation decreased below threshold levels of MYC. Thus, at the MYC threshold, there is a loss of its ability to maintain tumorigenesis, with associated shifts in gene and protein expression that reestablish cell cycle checkpoints, halt protein translation, and promote apoptosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5132-42
pubmed:meshHeading
pubmed-meshheading:18593912-Animals, pubmed-meshheading:18593912-Apoptosis, pubmed-meshheading:18593912-Cell Cycle, pubmed-meshheading:18593912-Cell Line, Tumor, pubmed-meshheading:18593912-Cluster Analysis, pubmed-meshheading:18593912-Disease Progression, pubmed-meshheading:18593912-Gene Expression Profiling, pubmed-meshheading:18593912-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18593912-Gene Regulatory Networks, pubmed-meshheading:18593912-Genomics, pubmed-meshheading:18593912-Mice, pubmed-meshheading:18593912-Mice, Transgenic, pubmed-meshheading:18593912-Neoplasms, pubmed-meshheading:18593912-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:18593912-Proteomics, pubmed-meshheading:18593912-Proto-Oncogene Proteins c-myc, pubmed-meshheading:18593912-Tumor Burden
pubmed:year
2008
pubmed:articleTitle
Genomic and proteomic analysis reveals a threshold level of MYC required for tumor maintenance.
pubmed:affiliation
Department of Medicine and Pathology, Division of Medical Oncology, Stanford University School of Medicine, Stanford University, Stanford, California 94305, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural