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Article: Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis

TitleDifferential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research.
Citation
Clinical Cancer Research, 2010, v. 16 n. 9, p. 2529-2539 How to Cite?
AbstractPurpose: Aberrant overexpression of growth factor receptor - bound protein 7 (GRB7) and its variant GRB7v has been found in numerous human cancers. The goal of this study was to characterize the functions of GRB7 and GRB7v in the ovarian carcinogenesis and to investigate the differential roles of GRB7 and GRB7v in the modulation of signaling pathways. Experimental Design: Quantitative reverse transcription - PCR, Western blot, and immunohistochemical analyses were used to evaluate the levels of GRB7 and GRB7v. The cellular localization, functions, and signaling pathways regulated by GRB7 and GRB7v were investigated by enforced expression of GRB7 and GRB7v. Results: Quantitative reverse transcription - PCR and Western blot analyses showed that GRB7 and GRB7v were frequently upregulated in ovarian cancer samples. The overexpressed GRB7 (P = 0.009) and GRB7v (P = 0.017) were significantly correlated with high-grade ovarian cancer. Immunohistochemical analysis on ovarian cancer tissue array confirmed that the upregulated GRB7 was significantly correlated with high-grade ovarian cancer (P = 0.001). Confocal microscopy analysis showed that GRB7 and GRB7v predominately localized in cytoplasm of ovarian cancer cells, consistent with their roles as signaling adaptors. Enforced expression of GRB7 promoted cell proliferation, migration, and invasion, whereas GRB7v only increased cell proliferation and anchorage-independent growth ability. With the treatment of specific kinase inhibitors, we showed that both GRB7 and GRB7v promoted cell proliferation through activating extracellular signal-regulated kinase signaling, whereas GRB7 enhanced cell migration/invasion by activating c-Jun NH2 terminal kinase signaling. Conclusions: Our studies implicate that the overexpressed GRB7 and GRB7v are associated with highgrade tumors and exert distinct tumorigenic functions through regulating different signaling pathways in ovarian cancer cells. ©2010 AACR.
Persistent Identifierhttp://hdl.handle.net/10722/148829
ISSN
2023 Impact Factor: 10.0
2023 SCImago Journal Rankings: 4.623
ISI Accession Number ID
Funding AgencyGrant Number
HKU Seed Funding Programme for Basic Research200811159046
Wong Check She Charitable Foundation
Funding Information:

HKU Seed Funding Programme for Basic Research grant 200811159046 and Wong Check She Charitable Foundation.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorWang, Yen_HK
dc.contributor.authorChan, DWen_HK
dc.contributor.authorLiu, VWSen_HK
dc.contributor.authorChiu, PMen_HK
dc.contributor.authorNgan, HYSen_HK
dc.date.accessioned2012-06-06T07:37:57Z-
dc.date.available2012-06-06T07:37:57Z-
dc.date.issued2010en_HK
dc.identifier.citationClinical Cancer Research, 2010, v. 16 n. 9, p. 2529-2539en_HK
dc.identifier.issn1078-0432en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148829-
dc.description.abstractPurpose: Aberrant overexpression of growth factor receptor - bound protein 7 (GRB7) and its variant GRB7v has been found in numerous human cancers. The goal of this study was to characterize the functions of GRB7 and GRB7v in the ovarian carcinogenesis and to investigate the differential roles of GRB7 and GRB7v in the modulation of signaling pathways. Experimental Design: Quantitative reverse transcription - PCR, Western blot, and immunohistochemical analyses were used to evaluate the levels of GRB7 and GRB7v. The cellular localization, functions, and signaling pathways regulated by GRB7 and GRB7v were investigated by enforced expression of GRB7 and GRB7v. Results: Quantitative reverse transcription - PCR and Western blot analyses showed that GRB7 and GRB7v were frequently upregulated in ovarian cancer samples. The overexpressed GRB7 (P = 0.009) and GRB7v (P = 0.017) were significantly correlated with high-grade ovarian cancer. Immunohistochemical analysis on ovarian cancer tissue array confirmed that the upregulated GRB7 was significantly correlated with high-grade ovarian cancer (P = 0.001). Confocal microscopy analysis showed that GRB7 and GRB7v predominately localized in cytoplasm of ovarian cancer cells, consistent with their roles as signaling adaptors. Enforced expression of GRB7 promoted cell proliferation, migration, and invasion, whereas GRB7v only increased cell proliferation and anchorage-independent growth ability. With the treatment of specific kinase inhibitors, we showed that both GRB7 and GRB7v promoted cell proliferation through activating extracellular signal-regulated kinase signaling, whereas GRB7 enhanced cell migration/invasion by activating c-Jun NH2 terminal kinase signaling. Conclusions: Our studies implicate that the overexpressed GRB7 and GRB7v are associated with highgrade tumors and exert distinct tumorigenic functions through regulating different signaling pathways in ovarian cancer cells. ©2010 AACR.en_HK
dc.languageeng-
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofClinical Cancer Researchen_HK
dc.subject.meshAlternative Splicing-
dc.subject.meshGRB7 Adaptor Protein - genetics - metabolism - physiology-
dc.subject.meshGreen Fluorescent Proteins - genetics - metabolism-
dc.subject.meshMitogen-Activated Protein Kinases - antagonists and inhibitors - metabolism-
dc.subject.meshOvarian Neoplasms - genetics - metabolism - pathology-
dc.titleDifferential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesisen_HK
dc.typeArticleen_HK
dc.identifier.emailChan, DW: dwchan@hku.hken_HK
dc.identifier.emailLiu, VWS: vwsliu@hkusua.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.authorityChan, DW=rp00543en_HK
dc.identifier.authorityLiu, VWS=rp00341en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-10-0018en_HK
dc.identifier.pmid20388850-
dc.identifier.scopuseid_2-s2.0-77951758017en_HK
dc.identifier.hkuros170528-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951758017&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume16en_HK
dc.identifier.issue9en_HK
dc.identifier.spage2529en_HK
dc.identifier.epage2539en_HK
dc.identifier.eissn1557-3265-
dc.identifier.isiWOS:000278596100008-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectFunctional characterization of GRB7 and its variant, GRB7v, in ovarian cancer-
dc.identifier.scopusauthoridWang, Y=55458221300en_HK
dc.identifier.scopusauthoridChan, DW=26533900600en_HK
dc.identifier.scopusauthoridLiu, VWS=7006405113en_HK
dc.identifier.scopusauthoridChiu, PM=24463308700en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.issnl1078-0432-

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