File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1593/neo.04454
- Scopus: eid_2-s2.0-18644367044
- PMID: 15967120
- WOS: WOS:000229011600014
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Gastrin-releasing peptide receptor mediates activation of the epidermal growth factor receptor in lung cancer cells
Title | Gastrin-releasing peptide receptor mediates activation of the epidermal growth factor receptor in lung cancer cells |
---|---|
Authors | |
Keywords | EGFR GRPR MAPK Non-small cell lung cancer Signal transduction |
Issue Date | 2005 |
Citation | Neoplasia, 2005, v. 7 n. 4, p. 426-431 How to Cite? |
Abstract | Gastrin-releasing peptide receptor (GRPR) and the epidermal growth factor receptor (EGFR) are expressed in several cancers including non-small cell lung cancer (NSCLC). Here we demonstrate the activation of EGFR by the GRPR ligand, gastrin-releasing peptide (GRP), in NSCLC cells. GRP induced rapid activation of p44/42 MAPK in lung cancer cells through EGFR. GRP-mediated activation of MAPK in NSCLC cells was abrogated by pretreatment with the anti-EGFR-neutralizing antibody, C225. Pretreatment of NSCLC cells with neutralizing antibodies to the EGFR ligands, TGF-α or HB-EGF, also decreased GRP-mediated MAPK activation. On matrix metalloproteinase (MMP) inhibition, GRP failed to activate MAPK in NSCLC cells. EGF and GRP both stimulated NSCLC proliferation, and inhibition of either EGFR or GRPR resulted in cell death. Combining a GRPR antagonist with the EGFR tyrosine kinase inhibitor, gefitinib, resulted in additive cytotoxic effects. Additive effects were seen at gefitinib concentrations from 1 to 18 μM, encompassing the ID50 values of both gefitinib-sensitive and gefitinib-resistant NSCLC cell lines. Because a major effect of GRPR appears to be promoting the release of EGFR ligand, this study suggests that a greater inhibition of cell proliferation may occur by abrogating EGFR ligand release in consort with inhibition of EGFR. Copyright © 2005 Neoplasia Press, Inc. All rights reserved. |
Persistent Identifier | http://hdl.handle.net/10722/194145 |
ISSN | 2014 Impact Factor: 4.252 2023 SCImago Journal Rankings: 1.887 |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Thomas, SM | - |
dc.contributor.author | Grandis, JR | - |
dc.contributor.author | Wentzel, AL | - |
dc.contributor.author | Gooding, WE | - |
dc.contributor.author | Lui, VWY | - |
dc.contributor.author | Siegfried, JM | - |
dc.date.accessioned | 2014-01-30T03:32:13Z | - |
dc.date.available | 2014-01-30T03:32:13Z | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Neoplasia, 2005, v. 7 n. 4, p. 426-431 | - |
dc.identifier.issn | 1522-8002 | - |
dc.identifier.uri | http://hdl.handle.net/10722/194145 | - |
dc.description.abstract | Gastrin-releasing peptide receptor (GRPR) and the epidermal growth factor receptor (EGFR) are expressed in several cancers including non-small cell lung cancer (NSCLC). Here we demonstrate the activation of EGFR by the GRPR ligand, gastrin-releasing peptide (GRP), in NSCLC cells. GRP induced rapid activation of p44/42 MAPK in lung cancer cells through EGFR. GRP-mediated activation of MAPK in NSCLC cells was abrogated by pretreatment with the anti-EGFR-neutralizing antibody, C225. Pretreatment of NSCLC cells with neutralizing antibodies to the EGFR ligands, TGF-α or HB-EGF, also decreased GRP-mediated MAPK activation. On matrix metalloproteinase (MMP) inhibition, GRP failed to activate MAPK in NSCLC cells. EGF and GRP both stimulated NSCLC proliferation, and inhibition of either EGFR or GRPR resulted in cell death. Combining a GRPR antagonist with the EGFR tyrosine kinase inhibitor, gefitinib, resulted in additive cytotoxic effects. Additive effects were seen at gefitinib concentrations from 1 to 18 μM, encompassing the ID50 values of both gefitinib-sensitive and gefitinib-resistant NSCLC cell lines. Because a major effect of GRPR appears to be promoting the release of EGFR ligand, this study suggests that a greater inhibition of cell proliferation may occur by abrogating EGFR ligand release in consort with inhibition of EGFR. Copyright © 2005 Neoplasia Press, Inc. All rights reserved. | - |
dc.language | eng | - |
dc.relation.ispartof | Neoplasia | - |
dc.subject | EGFR | - |
dc.subject | GRPR | - |
dc.subject | MAPK | - |
dc.subject | Non-small cell lung cancer | - |
dc.subject | Signal transduction | - |
dc.title | Gastrin-releasing peptide receptor mediates activation of the epidermal growth factor receptor in lung cancer cells | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1593/neo.04454 | - |
dc.identifier.pmid | 15967120 | - |
dc.identifier.scopus | eid_2-s2.0-18644367044 | - |
dc.identifier.volume | 7 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 426 | - |
dc.identifier.epage | 431 | - |
dc.identifier.isi | WOS:000229011600014 | - |
dc.identifier.issnl | 1476-5586 | - |