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Article: Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer

TitleAntitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer
Authors
Issue Date2007
Citation
Molecular Cancer Therapeutics, 2007, v. 6 n. 4, p. 1414-1424 How to Cite?
AbstractHead and neck squamous cell carcinoma (HNSCC) is characterized by epidermal growth factor receptor (EGFR) overexpression, where EGFR levels correlate with survival. To date, EGFR targeting has shown limited antitumor effects in head and neck cancer when administrated as monotherapy. We previously identified a gastrin-releasing peptide/ gastrin-releasing peptide receptor (GRP/GRPR) aurocrine regulatory pathway in HNSCC, where GRP stimulates Src-dependent cleavage of EGFR proligands with subsequent EGFR phosphorylation and mitogen-activated protein kinase (MAPK) activation. To determine whether GRPR targeting can enhance the antitumor efficacy of EGFR inhibition, we investigated the effects of a GRPR antagonist (PD176252) in conjunction with an EGFR tyrosine kinase inhibitor (erlotinib). Combined blockade of GRPR and EGFR pathways significantly inhibited HNSCC, but not immortalized mucosal epithelial cell, proliferation, invasion, and colony formation. In addition, the percentage of apoptotic cells increased upon combined inhibition. The enhanced antitumor efficacy was accompanied by increased expression of cleaved poly(ADP-ribose) polymerase (PARP) and decreased phospho-EGFR, phospho-MAPK, and proliferating cell nuclear antigen (PCNA). Using reverse-phase protein microarray (RPPA), we further detected decreased expression of phospho-c-Jun, phospho-p70S6K, and phospho-p38 with combined targeting. Cumulatively, these results suggest that GRPR targeting can enhance the antitumor effects of EGFR inhibitors in head and neck cancer. Copyright © 2007 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/194187
ISSN
2015 Impact Factor: 5.579
2015 SCImago Journal Rankings: 3.224
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Q-
dc.contributor.authorBhola, NE-
dc.contributor.authorLui, VWY-
dc.contributor.authorSiwak, DR-
dc.contributor.authorThomas, SM-
dc.contributor.authorGubish, CT-
dc.contributor.authorSiegfried, JM-
dc.contributor.authorMills, GB-
dc.contributor.authorShin, D-
dc.contributor.authorGrandis, JR-
dc.date.accessioned2014-01-30T03:32:16Z-
dc.date.available2014-01-30T03:32:16Z-
dc.date.issued2007-
dc.identifier.citationMolecular Cancer Therapeutics, 2007, v. 6 n. 4, p. 1414-1424-
dc.identifier.issn1535-7163-
dc.identifier.urihttp://hdl.handle.net/10722/194187-
dc.description.abstractHead and neck squamous cell carcinoma (HNSCC) is characterized by epidermal growth factor receptor (EGFR) overexpression, where EGFR levels correlate with survival. To date, EGFR targeting has shown limited antitumor effects in head and neck cancer when administrated as monotherapy. We previously identified a gastrin-releasing peptide/ gastrin-releasing peptide receptor (GRP/GRPR) aurocrine regulatory pathway in HNSCC, where GRP stimulates Src-dependent cleavage of EGFR proligands with subsequent EGFR phosphorylation and mitogen-activated protein kinase (MAPK) activation. To determine whether GRPR targeting can enhance the antitumor efficacy of EGFR inhibition, we investigated the effects of a GRPR antagonist (PD176252) in conjunction with an EGFR tyrosine kinase inhibitor (erlotinib). Combined blockade of GRPR and EGFR pathways significantly inhibited HNSCC, but not immortalized mucosal epithelial cell, proliferation, invasion, and colony formation. In addition, the percentage of apoptotic cells increased upon combined inhibition. The enhanced antitumor efficacy was accompanied by increased expression of cleaved poly(ADP-ribose) polymerase (PARP) and decreased phospho-EGFR, phospho-MAPK, and proliferating cell nuclear antigen (PCNA). Using reverse-phase protein microarray (RPPA), we further detected decreased expression of phospho-c-Jun, phospho-p70S6K, and phospho-p38 with combined targeting. Cumulatively, these results suggest that GRPR targeting can enhance the antitumor effects of EGFR inhibitors in head and neck cancer. Copyright © 2007 American Association for Cancer Research.-
dc.languageeng-
dc.relation.ispartofMolecular Cancer Therapeutics-
dc.titleAntitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1535-7163.MCT-06-0678-
dc.identifier.pmid17431120-
dc.identifier.scopuseid_2-s2.0-34248193845-
dc.identifier.volume6-
dc.identifier.issue4-
dc.identifier.spage1414-
dc.identifier.epage1424-
dc.identifier.isiWOS:000245939000026-

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