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Article: Mitogenic effects of gastrin-releasing peptide in head and neck squamous cancer cells are mediated by activation of the epidermal growth factor receptor

TitleMitogenic effects of gastrin-releasing peptide in head and neck squamous cancer cells are mediated by activation of the epidermal growth factor receptor
Authors
Issue Date2003
Citation
Oncogene, 2003, v. 22 n. 40, p. 6183-6193 How to Cite?
AbstractHead and neck squamous cell carcinomas (HNSCC) are characterized by upregulation of the epidermal growth factor receptor (EGFR), where EGFR serves as a potential therapeutic target. We previously reported that a gastrin-releasing peptide/gastrin-releasing peptide receptor (GRP/GRPR) autocrine growth pathway is activated early in HNSCC carcinogenesis. In the present study, we examined the mechanism of EGFR activation by GRP/GRPR in HNSCC proliferation. In HNSCC cells that express elevated levels of both GRPR and EGFR, we found that GRP induced rapid phosphorylation of EGFR as well as p44/42-MAPK activation. Using several EGFR-specific tyrosine kinase inhibitors and cells derived from EGFR knockout mice, we demonstrated that GRP-induced p44/42-MAPK activation was dependent upon EGFR activation. Further investigation demonstrated that cleavage of transforming growth factor-alpha (TGF-α) by matrix metalloproteinases mediated GRP-induced MAPK activation. In addition, HNSCC proliferation stimulated by GRP was eliminated upon specific inhibition of EGFR or MEK, and GRP failed to stimulate proliferation in EGFR-deficient cells. These results imply that the mitogenic effects of GRP in HNSCC are mediated by extracellular release of TGF-α and require the activation of an EGFR-dependent MEK/MAPK-dependent pathway.
Persistent Identifierhttp://hdl.handle.net/10722/194134
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLui, VWY-
dc.contributor.authorThomas, SM-
dc.contributor.authorZhang, Q-
dc.contributor.authorWentzel, AL-
dc.contributor.authorSiegfried, JM-
dc.contributor.authorLi, JY-
dc.contributor.authorGrandis, JR-
dc.date.accessioned2014-01-30T03:32:12Z-
dc.date.available2014-01-30T03:32:12Z-
dc.date.issued2003-
dc.identifier.citationOncogene, 2003, v. 22 n. 40, p. 6183-6193-
dc.identifier.issn0950-9232-
dc.identifier.urihttp://hdl.handle.net/10722/194134-
dc.description.abstractHead and neck squamous cell carcinomas (HNSCC) are characterized by upregulation of the epidermal growth factor receptor (EGFR), where EGFR serves as a potential therapeutic target. We previously reported that a gastrin-releasing peptide/gastrin-releasing peptide receptor (GRP/GRPR) autocrine growth pathway is activated early in HNSCC carcinogenesis. In the present study, we examined the mechanism of EGFR activation by GRP/GRPR in HNSCC proliferation. In HNSCC cells that express elevated levels of both GRPR and EGFR, we found that GRP induced rapid phosphorylation of EGFR as well as p44/42-MAPK activation. Using several EGFR-specific tyrosine kinase inhibitors and cells derived from EGFR knockout mice, we demonstrated that GRP-induced p44/42-MAPK activation was dependent upon EGFR activation. Further investigation demonstrated that cleavage of transforming growth factor-alpha (TGF-α) by matrix metalloproteinases mediated GRP-induced MAPK activation. In addition, HNSCC proliferation stimulated by GRP was eliminated upon specific inhibition of EGFR or MEK, and GRP failed to stimulate proliferation in EGFR-deficient cells. These results imply that the mitogenic effects of GRP in HNSCC are mediated by extracellular release of TGF-α and require the activation of an EGFR-dependent MEK/MAPK-dependent pathway.-
dc.languageeng-
dc.relation.ispartofOncogene-
dc.titleMitogenic effects of gastrin-releasing peptide in head and neck squamous cancer cells are mediated by activation of the epidermal growth factor receptor-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.onc.1206720-
dc.identifier.pmid13679857-
dc.identifier.scopuseid_2-s2.0-0142025133-
dc.identifier.volume22-
dc.identifier.issue40-
dc.identifier.spage6183-
dc.identifier.epage6193-
dc.identifier.isiWOS:000185506200008-

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