Linked Life Data

15960973

Source:http://linkedlifedata.com/resource/pubmed/id/15960973

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-6-17
pubmed:abstractText
Activating mutations of RAS frequently occur in subsets of human cancers, indicating that RAS activation is important for tumorigenesis. However, a large proportion of these cancers still retain wild-type RAS alleles, suggesting that either the RAS pathway is activated in a distinct manner or another pathway is deregulated. To uncover novel tumor-suppressor genes, we screened an RNA-interference library for knockdown constructs that transform human primary cells in the absence of ectopically introduced oncogenic RAS. Here we report the identification of PITX1, whose inhibition induces the RAS pathway and tumorigenicity. Interestingly, we observed low expression of PITX1 in prostate and bladder tumors and in colon cancer cell lines containing wild-type RAS. Restoration of PITX1 in the colon cancer cells inhibited tumorigenicity in a wild-type RAS-dependent manner. Finally, we identified RASAL1, a RAS-GTPase-activating protein, as a transcription target through which PITX1 affects RAS function. Thus, PITX1 suppresses tumorigenicity by downregulating the RAS pathway through RASAL1.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0092-8674
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
849-58
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15960973-Animals, pubmed-meshheading:15960973-Caco-2 Cells, pubmed-meshheading:15960973-Cell Line, Tumor, pubmed-meshheading:15960973-Gene Expression Regulation, pubmed-meshheading:15960973-Gene Library, pubmed-meshheading:15960973-Genes, Tumor Suppressor, pubmed-meshheading:15960973-Genetic Testing, pubmed-meshheading:15960973-Genetic Vectors, pubmed-meshheading:15960973-HeLa Cells, pubmed-meshheading:15960973-Homeodomain Proteins, pubmed-meshheading:15960973-Humans, pubmed-meshheading:15960973-Mice, pubmed-meshheading:15960973-Mice, Nude, pubmed-meshheading:15960973-Paired Box Transcription Factors, pubmed-meshheading:15960973-Phenotype, pubmed-meshheading:15960973-RNA Interference, pubmed-meshheading:15960973-Transcription Factors, pubmed-meshheading:15960973-ras Proteins
pubmed:year
2005
pubmed:articleTitle
A genetic screen identifies PITX1 as a suppressor of RAS activity and tumorigenicity.
pubmed:affiliation
Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't