File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis
  • Basic View
  • Metadata View
  • XML View
TitleDifferential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis
 
AuthorsWang, Y1
Chan, DW1
Liu, VWS1
Chiu, PM1
Ngan, HYS1
 
Issue Date2010
 
PublisherAmerican Association for Cancer Research.
 
CitationClinical Cancer Research, 2010, v. 16 n. 9, p. 2529-2539 [How to Cite?]
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-10-0018
 
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.
 
ISSN1078-0432
2012 Impact Factor: 7.837
2012 SCImago Journal Rankings: 3.798
 
DOIhttp://dx.doi.org/10.1158/1078-0432.CCR-10-0018
 
ISI Accession Number IDWOS:000278596100008
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorWang, Y
 
dc.contributor.authorChan, DW
 
dc.contributor.authorLiu, VWS
 
dc.contributor.authorChiu, PM
 
dc.contributor.authorNgan, HYS
 
dc.date.accessioned2012-06-06T07:37:57Z
 
dc.date.available2012-06-06T07:37:57Z
 
dc.date.issued2010
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationClinical Cancer Research, 2010, v. 16 n. 9, p. 2529-2539 [How to Cite?]
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-10-0018
 
dc.identifier.doihttp://dx.doi.org/10.1158/1078-0432.CCR-10-0018
 
dc.identifier.eissn1557-3265
 
dc.identifier.epage2539
 
dc.identifier.hkuros170528
 
dc.identifier.isiWOS:000278596100008
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.

 
dc.identifier.issn1078-0432
2012 Impact Factor: 7.837
2012 SCImago Journal Rankings: 3.798
 
dc.identifier.issue9
 
dc.identifier.pmid20388850
 
dc.identifier.scopuseid_2-s2.0-77951758017
 
dc.identifier.spage2529
 
dc.identifier.urihttp://hdl.handle.net/10722/148829
 
dc.identifier.volume16
 
dc.languageeng
 
dc.publisherAmerican Association for Cancer Research.
 
dc.publisher.placeUnited States
 
dc.relation.ispartofClinical Cancer Research
 
dc.relation.referencesReferences in Scopus
 
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 carcinogenesis
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Wang, Y</contributor.author>
<contributor.author>Chan, DW</contributor.author>
<contributor.author>Liu, VWS</contributor.author>
<contributor.author>Chiu, PM</contributor.author>
<contributor.author>Ngan, HYS</contributor.author>
<date.accessioned>2012-06-06T07:37:57Z</date.accessioned>
<date.available>2012-06-06T07:37:57Z</date.available>
<date.issued>2010</date.issued>
<identifier.citation>Clinical Cancer Research, 2010, v. 16 n. 9, p. 2529-2539</identifier.citation>
<identifier.issn>1078-0432</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/148829</identifier.uri>
<description.abstract>Purpose: 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. &#169;2010 AACR.</description.abstract>
<language>eng</language>
<publisher>American Association for Cancer Research.</publisher>
<relation.ispartof>Clinical Cancer Research</relation.ispartof>
<subject.mesh>Alternative Splicing</subject.mesh>
<subject.mesh>GRB7 Adaptor Protein - genetics - metabolism - physiology</subject.mesh>
<subject.mesh>Green Fluorescent Proteins - genetics - metabolism</subject.mesh>
<subject.mesh>Mitogen-Activated Protein Kinases - antagonists and inhibitors - metabolism</subject.mesh>
<subject.mesh>Ovarian Neoplasms - genetics - metabolism - pathology</subject.mesh>
<title>Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis</title>
<type>Article</type>
<description.nature>link_to_subscribed_fulltext</description.nature>
<identifier.doi>10.1158/1078-0432.CCR-10-0018</identifier.doi>
<identifier.pmid>20388850</identifier.pmid>
<identifier.scopus>eid_2-s2.0-77951758017</identifier.scopus>
<identifier.hkuros>170528</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-77951758017&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>16</identifier.volume>
<identifier.issue>9</identifier.issue>
<identifier.spage>2529</identifier.spage>
<identifier.epage>2539</identifier.epage>
<identifier.eissn>1557-3265</identifier.eissn>
<identifier.isi>WOS:000278596100008</identifier.isi>
<publisher.place>United States</publisher.place>
</item>
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine