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- Publisher Website: 10.1158/1535-7163.MCT-06-0678
- Scopus: eid_2-s2.0-34248193845
- PMID: 17431120
- WOS: WOS:000245939000026
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Article: Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer
Title | Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer |
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Authors | |
Issue Date | 2007 |
Citation | Molecular Cancer Therapeutics, 2007, v. 6 n. 4, p. 1414-1424 How to Cite? |
Abstract | Head 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 Identifier | http://hdl.handle.net/10722/194187 |
ISSN | 2023 Impact Factor: 5.3 2023 SCImago Journal Rankings: 2.270 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Zhang, Q | - |
dc.contributor.author | Bhola, NE | - |
dc.contributor.author | Lui, VWY | - |
dc.contributor.author | Siwak, DR | - |
dc.contributor.author | Thomas, SM | - |
dc.contributor.author | Gubish, CT | - |
dc.contributor.author | Siegfried, JM | - |
dc.contributor.author | Mills, GB | - |
dc.contributor.author | Shin, D | - |
dc.contributor.author | Grandis, JR | - |
dc.date.accessioned | 2014-01-30T03:32:16Z | - |
dc.date.available | 2014-01-30T03:32:16Z | - |
dc.date.issued | 2007 | - |
dc.identifier.citation | Molecular Cancer Therapeutics, 2007, v. 6 n. 4, p. 1414-1424 | - |
dc.identifier.issn | 1535-7163 | - |
dc.identifier.uri | http://hdl.handle.net/10722/194187 | - |
dc.description.abstract | Head 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.language | eng | - |
dc.relation.ispartof | Molecular Cancer Therapeutics | - |
dc.title | Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1158/1535-7163.MCT-06-0678 | - |
dc.identifier.pmid | 17431120 | - |
dc.identifier.scopus | eid_2-s2.0-34248193845 | - |
dc.identifier.volume | 6 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 1414 | - |
dc.identifier.epage | 1424 | - |
dc.identifier.isi | WOS:000245939000026 | - |
dc.identifier.issnl | 1535-7163 | - |