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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-4-11
pubmed:abstractText
Tumor hypoxia is associated with a malignant phenotype of cancer cells and poor patient prognosis. To investigate the role of hypoxia in tumor progression, we studied the effects of hypoxia in the A549 lung adenocarcinoma cell line. First, we showed that hypoxic treatment decreased cell-cell adhesion and induced a scattering of cancer cells. Concomitant with these morphological changes, the motility of cancer cells was increased, as demonstrated by the Boyden chamber assay. Then, we used oligonucleotide array analyses to identify the genes causally related to the hypoxia-induced motile phenotype. The results showed that the expression of approximately 100 genes was induced more than 5-fold by hypoxia. These included (among others) epidermal growth factor receptor (EGFR), as well as other well-known hypoxia-induced genes, such as vascular endothelial growth factor. Immunohistochemical analyses of primary lung adenocarcinomas confirmed the induction of EGFR in tumor cells in the vicinity of necrotic areas, a histological indicator of tumor hypoxia. Remarkably, the EGFR inhibitor AG1478 (10 microM) completely blocked the increased cell motility induced by hypoxia. Thus, the present study demonstrates the importance of the EGFR pathway in the increased motility of cancer cells that occurs in a hypoxic tumor environment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1347-9032
pubmed:author
pubmed:issnType
Print
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
506-11
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Hypoxia increases the motility of lung adenocarcinoma cell line A549 via activation of the epidermal growth factor receptor pathway.
pubmed:affiliation
Department of Human Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't