Linked Life Data

19934338

Source:http://linkedlifedata.com/resource/pubmed/id/19934338

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-12-4
pubmed:abstractText
Overexpression of the receptor tyrosine kinase EphA2 occurs in non-small cell lung cancer (NSCLC) and a number of other human cancers. This overexpression correlates with a poor prognosis, smoking, and the presence of Kirsten rat sarcoma (K-Ras) mutations in NSCLC. In other cancers, EphA2 has been implicated in migration and metastasis. To determine if EphA2 can promote NSCLC progression, we examined the relationship of EphA2 with proliferation and migration in cell lines and with metastases in patient tumors. We also examined potential mechanisms involving AKT, Src, focal adhesion kinase, Rho guanosine triphosphatases (GTPase), and extracellular signal-regulated kinase (ERK)-1/2. Knockdown of EphA2 in NSCLC cell lines decreased proliferation (colony size) by 20% to 70% in four of five cell lines (P < 0. 04) and cell migration by 7% to 75% in five of six cell lines (P < 0. 03). ERK1/2 activation correlated with effects on proliferation, and inhibition of ERK1/2 activation also suppressed proliferation. In accordance with the in vitro data, high tumor expression of EphA2 was an independent prognostic factor in time to recurrence (P = 0.057) and time to metastases (P = 0.046) of NSCLC patients. We also examined EphA2 expression in the putative premalignant lung lesion, atypical adenomatous hyperplasia, and the noninvasive bronchioloalveolar component of adenocarcinoma because K-Ras mutations occur in atypical adenomatous hyperplasia and are common in lung adenocarcinomas. Both preinvasive lesion types expressed EphA2, showing its expression in the early pathogenesis of lung adenocarcinoma. Our data suggest that EphA2 may be a promising target for treating and preventing NSCLC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1940-6215
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1039-49
pubmed:dateRevised
2010-9-16
pubmed:meshHeading
pubmed-meshheading:19934338-Apoptosis, pubmed-meshheading:19934338-Blotting, Western, pubmed-meshheading:19934338-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:19934338-Cell Adhesion, pubmed-meshheading:19934338-Cell Cycle, pubmed-meshheading:19934338-Cell Movement, pubmed-meshheading:19934338-Cell Proliferation, pubmed-meshheading:19934338-Disease Progression, pubmed-meshheading:19934338-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:19934338-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:19934338-Humans, pubmed-meshheading:19934338-Immunoenzyme Techniques, pubmed-meshheading:19934338-Immunoprecipitation, pubmed-meshheading:19934338-Lung Neoplasms, pubmed-meshheading:19934338-Neoplasm Recurrence, Local, pubmed-meshheading:19934338-RNA, Messenger, pubmed-meshheading:19934338-Receptor, EphA2, pubmed-meshheading:19934338-Receptor, Epidermal Growth Factor, pubmed-meshheading:19934338-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19934338-Survival Rate, pubmed-meshheading:19934338-Tissue Array Analysis
pubmed:year
2009
pubmed:articleTitle
EphA2 in the early pathogenesis and progression of non-small cell lung cancer.
pubmed:affiliation
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural