Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-9-6
pubmed:abstractText
Epidermal growth factor receptor (HER1/EGFR)-mediated signal transduction pathways are important in cellular response to ionizing radiation. High HER1/EGFR expression on cancer cells may contribute to radioresistance. In this pre-clinical study, we evaluated the radiosensitizing effect of erlotinib, a small molecule HER1/EGFR inhibitor in three human cancer cell lines with different HER1/EGFR expression--A431 (very high expression), H157 (moderate expression) and H460 (low expression). Our results demonstrated that A431 was the most radioresistant, while H460 was the most radiosensitive. However, A431 cells were the most sensitive to erlotinib (IC50 = 300 nM) and H460 cells the most resistant (IC50 = 8 microM). H157 had intermediate sensitivity to radiation and erlotinib (IC50 = 3 microM). With 300 nM erlotinib, the radiation dose enhancement ratios (DER) were 1.40, 1.17 and 1.04 in A431, H157 and H460, respectively. Treatment with erlotinib for 24 hr at 300 nM increased G1 arrest by 18.6, 2.0 and 4.8% in A431, H157 and H460, respectively. Erlotinib-induced apoptosis was augmented by radiation in A431 cells only. In conclusion, high HER1/EGFR expression may result in a high degree of radiosensitization with erlotinib combined with radiation. The extent of erlotinib-induced radiosensitization was proportional to HER1/EGFR expression, as well as autophosphorylation of the human epidermal growth factor receptor (HER1/EGFR).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0301-1208
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
358-65
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Correlation of HER1/EGFR expression and degree of radiosensitizing effect of the HER1/EGFR-tyrosine kinase inhibitor erlotinib.
pubmed:affiliation
Department of Radiation Oncology, Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center, Dallas 75390-9187, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural