Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-5-13
pubmed:abstractText
We determined whether phosphorylated epidermal growth factor receptor (EGFR) expressed on tumor-associated endothelial cells is a primary target for therapy with EGFR tyrosine kinase inhibitors (TKIs). Human colon cancer cells SW620CE2 (parental) that do not express EGFR or human epidermal growth factor receptor 2 (HER2) but express transforming growth factor alpha (TGF-alpha) were transduced with a lentivirus carrying nontargeting small hairpin RNA (shRNA) or TGF-alpha shRNA. The cell lines were implanted into the cecum of nude mice. Two weeks later, treatment began with saline, 4-[R]-phenethylamino-6-[hydroxyl] phenyl-7H-pyrrolo [2,3-D]-pyrimidine (PKI166), or irinotecan. Endothelial cells in parental and nontargeting shRNA tumors expressed phosphorylated EGFR. Therapy with PKI166 alone or with irinotecan produced apoptosis of these endothelial cells and necrosis of the EGFR-negative tumors. Endothelial cells in tumors that did not express TGF-alpha did not express EGFR, and these tumors were resistant to treatment with PKI166. The response of neoplasms to EGFR antagonists has been correlated with EGFR mutations, HER2 expression, Akt activation, and EGFR gene copy number. Our present data using colon cancer cells that do not express EGFR or HER2 suggest that the expression of TGF-alpha by tumor cells leading to the activation of EGFR in tumor-associated endothelial cells is a major determinant for the susceptibility of neoplasms to therapy by specific EGFR-TKI.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-10728704, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-10850439, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-10999768, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-11330643, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-11706401, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-11905606, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-12213721, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-12360276, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-12420216, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-12492492, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-12631626, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-12778135, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-12885912, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-14570950, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-14967450, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15118073, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15118125, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15172974, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15205332, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15256466, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15329413, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15520205, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15677699, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15681531, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15710947, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15753456, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15867367, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-15948138, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16000591, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16014882, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16014883, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16026649, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16051952, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16336755, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16432168, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16757703, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16820093, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-1688381, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16900530, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-16926635, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-17148668, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-17234777, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-17296817, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-17406029, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-17409287, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-3349467, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-8391303, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-9346240, http://linkedlifedata.com/resource/pubmed/commentcorrection/18472966-9755233
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin, http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/ERBB2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/PKI 166, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines, http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2, http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase I Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha, http://linkedlifedata.com/resource/pubmed/chemical/irinotecan
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1476-5586
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
489-500
pubmed:dateRevised
2010-11-18
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