Linked Life Data

19966867

Source:http://linkedlifedata.com/resource/pubmed/id/19966867

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-3-11
pubmed:databankReference
pubmed:abstractText
DNA amplifications, leading to the overexpression of oncogenes, are a cardinal feature of lung cancer and directly contribute to its pathogenesis. To uncover such novel alterations, we performed an array-based comparative genomic hybridization survey of 128 non-small-cell lung cancer cell lines and tumors. Prominent among our findings, we identified recurrent high-level amplification at cytoband 22q11.21 in 3% of lung cancer specimens, with another 11% of specimens exhibiting low-level gain spanning that locus. The 22q11.21 amplicon core contained eight named genes, only four of which were overexpressed (by transcript profiling) when amplified. Among these, CRKL encodes an adapter protein functioning in signal transduction, best known as a substrate of the BCR-ABL kinase in chronic myelogenous leukemia. RNA-interference-mediated knockdown of CRKL in lung cancer cell lines with (but not without) amplification led to significantly decreased cell proliferation, cell-cycle progression, cell survival, and cell motility and invasion. In addition, overexpression of CRKL in immortalized human bronchial epithelial cells led to enhanced growth factor-independent cell growth. Our findings indicate that amplification and resultant overexpression of CRKL contribute to diverse oncogenic phenotypes in lung cancer, with implications for targeted therapy, and highlight a role of adapter proteins as primary genetic drivers of tumorigenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1421-30
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed-meshheading:19966867-Adaptor Proteins, Signal Transducing, pubmed-meshheading:19966867-Blotting, Western, pubmed-meshheading:19966867-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:19966867-Cell Line, Tumor, pubmed-meshheading:19966867-Cell Movement, pubmed-meshheading:19966867-Cell Proliferation, pubmed-meshheading:19966867-Cell Survival, pubmed-meshheading:19966867-Chromosomes, Human, Pair 22, pubmed-meshheading:19966867-Comparative Genomic Hybridization, pubmed-meshheading:19966867-Gene Amplification, pubmed-meshheading:19966867-Gene Expression Profiling, pubmed-meshheading:19966867-Humans, pubmed-meshheading:19966867-In Situ Hybridization, Fluorescence, pubmed-meshheading:19966867-Lung Neoplasms, pubmed-meshheading:19966867-Nuclear Proteins, pubmed-meshheading:19966867-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19966867-RNA Interference
pubmed:year
2010
pubmed:articleTitle
Genomic and functional analysis identifies CRKL as an oncogene amplified in lung cancer.
pubmed:affiliation
Department of Pathology, Stanford University, Stanford, CA 94305-5176, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural