Article: Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis
| Title | Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Wang, Y1 Chan, DW1 Liu, VWS1 Chiu, PM1 Ngan, HYS1 | ||||||
| Issue Date | 2010 | ||||||
| Publisher | American Association for Cancer Research. | ||||||
| Citation | Clinical 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 | ||||||
| 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. ©2010 AACR. | ||||||
| ISSN | 1078-0432 2011 Impact Factor: 7.742 2011 SCImago Journal Rankings: 1.066 | ||||||
| DOI | http://dx.doi.org/10.1158/1078-0432.CCR-10-0018 | ||||||
| ISI Accession Number ID | WOS:000278596100008
Funding Information: HKU Seed Funding Programme for Basic Research grant 200811159046 and Wong Check She Charitable Foundation. | ||||||
| References | References in Scopus | ||||||
| Grants | Functional characterization of GRB7 and its variant, GRB7v, in ovarian cancer |
| dc.contributor.author | Wang, Y | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Chan, DW | ||||||
| dc.contributor.author | Liu, VWS | ||||||
| dc.contributor.author | Chiu, PM | ||||||
| dc.contributor.author | Ngan, HYS | ||||||
| dc.date.accessioned | 2012-06-06T07:37:57Z | ||||||
| dc.date.available | 2012-06-06T07:37:57Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.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. ©2010 AACR. | ||||||
| dc.description.grant | Functional characterization of GRB7 and its variant, GRB7v, in ovarian cancer | ||||||
| dc.description.grantcode | 99856 | ||||||
| dc.description.nature | link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Clinical 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.doi | http://dx.doi.org/10.1158/1078-0432.CCR-10-0018 | ||||||
| dc.identifier.epage | 2539 | ||||||
| dc.identifier.hkuros | 170528 | ||||||
| dc.identifier.isi | WOS:000278596100008
Funding Information: HKU Seed Funding Programme for Basic Research grant 200811159046 and Wong Check She Charitable Foundation. | ||||||
| dc.identifier.issn | 1078-0432 2011 Impact Factor: 7.742 2011 SCImago Journal Rankings: 1.066 | ||||||
| dc.identifier.issue | 9 | ||||||
| dc.identifier.pmid | 20388850 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77951758017 | ||||||
| dc.identifier.spage | 2529 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/148829 | ||||||
| dc.identifier.volume | 16 | ||||||
| dc.language | eng | ||||||
| dc.publisher | American Association for Cancer Research. | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Clinical Cancer Research | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Alternative Splicing | ||||||
| dc.subject.mesh | GRB7 Adaptor Protein - genetics - metabolism - physiology | ||||||
| dc.subject.mesh | Green Fluorescent Proteins - genetics - metabolism | ||||||
| dc.subject.mesh | Mitogen-Activated Protein Kinases - antagonists and inhibitors - metabolism | ||||||
| dc.subject.mesh | Ovarian Neoplasms - genetics - metabolism - pathology | ||||||
| dc.title | Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine