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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
KeywordsEGFR transactivation
G-protein-coupled receptor
GRPR
Head and neck cancer
TGF-α
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
2023 Impact Factor: 6.9
2023 SCImago Journal Rankings: 2.334
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.subjectEGFR transactivation-
dc.subjectG-protein-coupled receptor-
dc.subjectGRPR-
dc.subjectHead and neck cancer-
dc.subjectTGF-α-
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-
dc.identifier.issnl0950-9232-

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