File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers
  • Basic View
  • Metadata View
  • XML View
TitleOverexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers
 
AuthorsJiang, L1 4
Siu, MKY1
Wong, OGW1
Tam, KF1
Lam, EWF2
Ngan, HYS1
Le, XF3
Wong, ESY1
Chan, HY1
Cheung, ANY1
 
Issue Date2010
 
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
 
CitationMolecular Cancer, 2010, v. 9 [How to Cite?]
DOI: http://dx.doi.org/10.1186/1476-4598-9-318
 
AbstractBackground: FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) is a member of the POK (POZ and Kruppel) family of transcription factors and play important roles in cellular differentiation and oncogenesis. Recent evidence suggests that FBI-1 is expressed at high levels in a subset of human lymphomas and some epithelial solid tumors. However, the function of FBI-1 in human ovarian cancers remains elusive.Results: In this study, we investigated the role of FBI-1 in human ovarian cancers, in particularly, its function in cancer cell invasion via modulating membrane type 1-matrix metalloproteinase (MT1-MMP). Significantly higher FBI-1 protein and mRNA expression levels were demonstrated in ovarian cancers samples and cell lines compared with borderline tumors and benign cystadenomas. Increased FBI-1 mRNA expression was correlated significantly with gene amplification (P = 0.037). Moreover, higher FBI-1 expression was found in metastatic foci (P = 0.036) and malignant ascites (P = 0.021), and was significantly associated with advanced stage (P = 0.012), shorter overall survival (P = 0.032) and disease-free survival (P = 0.016). In vitro, overexpressed FBI-1 significantly enhanced cell migration and invasion both in OVCA 420 and SKOV-3 ovarian carcinoma cells, irrespective of p53 status, accompanied with elevated expression of MT1-MMP, but not MMP-2 or TIMP-2. Moreover, knockdown of MT1-MMP abolished FBI-1-mediated cell migration and invasion. Conversely, stable knockdown of FBI-1 remarkably reduced the motility of these cells with decreased expression of MT1-MMP. Promoter assay and chromatin immunoprecipitation study indicated that FBI-1 could directly interact with the promoter spanning ~600bp of the 5'-flanking sequence of MT1-MMP and enhanced its expression in a dose-dependent manner. Furthermore, stable knockdown and ectopic expression of FBI-1 decreased and increased cell proliferation respectively in OVCA 420, but not in the p53 null SKOV-3 cells.Conclusions: Our results suggested an important role of FBI-1 in ovarian cancer cell proliferation, cell mobility, and invasiveness, and that FBI-1 can be a potential target of chemotherapy. © 2010 Jiang et al; licensee BioMed Central Ltd.
 
ISSN1476-4598
2013 Impact Factor: 5.397
2013 SCImago Journal Rankings: 2.876
 
DOIhttp://dx.doi.org/10.1186/1476-4598-9-318
 
PubMed Central IDPMC3022670
 
ISI Accession Number IDWOS:000286383600001
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorJiang, L
 
dc.contributor.authorSiu, MKY
 
dc.contributor.authorWong, OGW
 
dc.contributor.authorTam, KF
 
dc.contributor.authorLam, EWF
 
dc.contributor.authorNgan, HYS
 
dc.contributor.authorLe, XF
 
dc.contributor.authorWong, ESY
 
dc.contributor.authorChan, HY
 
dc.contributor.authorCheung, ANY
 
dc.date.accessioned2011-09-23T06:01:56Z
 
dc.date.available2011-09-23T06:01:56Z
 
dc.date.issued2010
 
dc.description.abstractBackground: FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) is a member of the POK (POZ and Kruppel) family of transcription factors and play important roles in cellular differentiation and oncogenesis. Recent evidence suggests that FBI-1 is expressed at high levels in a subset of human lymphomas and some epithelial solid tumors. However, the function of FBI-1 in human ovarian cancers remains elusive.Results: In this study, we investigated the role of FBI-1 in human ovarian cancers, in particularly, its function in cancer cell invasion via modulating membrane type 1-matrix metalloproteinase (MT1-MMP). Significantly higher FBI-1 protein and mRNA expression levels were demonstrated in ovarian cancers samples and cell lines compared with borderline tumors and benign cystadenomas. Increased FBI-1 mRNA expression was correlated significantly with gene amplification (P = 0.037). Moreover, higher FBI-1 expression was found in metastatic foci (P = 0.036) and malignant ascites (P = 0.021), and was significantly associated with advanced stage (P = 0.012), shorter overall survival (P = 0.032) and disease-free survival (P = 0.016). In vitro, overexpressed FBI-1 significantly enhanced cell migration and invasion both in OVCA 420 and SKOV-3 ovarian carcinoma cells, irrespective of p53 status, accompanied with elevated expression of MT1-MMP, but not MMP-2 or TIMP-2. Moreover, knockdown of MT1-MMP abolished FBI-1-mediated cell migration and invasion. Conversely, stable knockdown of FBI-1 remarkably reduced the motility of these cells with decreased expression of MT1-MMP. Promoter assay and chromatin immunoprecipitation study indicated that FBI-1 could directly interact with the promoter spanning ~600bp of the 5'-flanking sequence of MT1-MMP and enhanced its expression in a dose-dependent manner. Furthermore, stable knockdown and ectopic expression of FBI-1 decreased and increased cell proliferation respectively in OVCA 420, but not in the p53 null SKOV-3 cells.Conclusions: Our results suggested an important role of FBI-1 in ovarian cancer cell proliferation, cell mobility, and invasiveness, and that FBI-1 can be a potential target of chemotherapy. © 2010 Jiang et al; licensee BioMed Central Ltd.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationMolecular Cancer, 2010, v. 9 [How to Cite?]
DOI: http://dx.doi.org/10.1186/1476-4598-9-318
 
dc.identifier.doihttp://dx.doi.org/10.1186/1476-4598-9-318
 
dc.identifier.hkuros192471
 
dc.identifier.isiWOS:000286383600001
 
dc.identifier.issn1476-4598
2013 Impact Factor: 5.397
2013 SCImago Journal Rankings: 2.876
 
dc.identifier.pmcidPMC3022670
 
dc.identifier.pmid21176152
 
dc.identifier.scopuseid_2-s2.0-78650278812
 
dc.identifier.urihttp://hdl.handle.net/10722/139933
 
dc.identifier.volume9
 
dc.languageeng
 
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofMolecular Cancer
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.rightsMolecular Cancer. Copyright © BioMed Central Ltd.
 
dc.subject.meshCell Line, Tumor
 
dc.subject.meshDNA-Binding Proteins - genetics - metabolism
 
dc.subject.meshMatrix Metalloproteinase 14 - genetics - metabolism
 
dc.subject.meshOvarian Neoplasms - enzymology - pathology
 
dc.subject.meshTranscription Factors - genetics - metabolism
 
dc.titleOverexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Jiang, L</contributor.author>
<contributor.author>Siu, MKY</contributor.author>
<contributor.author>Wong, OGW</contributor.author>
<contributor.author>Tam, KF</contributor.author>
<contributor.author>Lam, EWF</contributor.author>
<contributor.author>Ngan, HYS</contributor.author>
<contributor.author>Le, XF</contributor.author>
<contributor.author>Wong, ESY</contributor.author>
<contributor.author>Chan, HY</contributor.author>
<contributor.author>Cheung, ANY</contributor.author>
<date.accessioned>2011-09-23T06:01:56Z</date.accessioned>
<date.available>2011-09-23T06:01:56Z</date.available>
<date.issued>2010</date.issued>
<identifier.citation>Molecular Cancer, 2010, v. 9</identifier.citation>
<identifier.issn>1476-4598</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/139933</identifier.uri>
<description.abstract>Background: FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) is a member of the POK (POZ and Kruppel) family of transcription factors and play important roles in cellular differentiation and oncogenesis. Recent evidence suggests that FBI-1 is expressed at high levels in a subset of human lymphomas and some epithelial solid tumors. However, the function of FBI-1 in human ovarian cancers remains elusive.Results: In this study, we investigated the role of FBI-1 in human ovarian cancers, in particularly, its function in cancer cell invasion via modulating membrane type 1-matrix metalloproteinase (MT1-MMP). Significantly higher FBI-1 protein and mRNA expression levels were demonstrated in ovarian cancers samples and cell lines compared with borderline tumors and benign cystadenomas. Increased FBI-1 mRNA expression was correlated significantly with gene amplification (P = 0.037). Moreover, higher FBI-1 expression was found in metastatic foci (P = 0.036) and malignant ascites (P = 0.021), and was significantly associated with advanced stage (P = 0.012), shorter overall survival (P = 0.032) and disease-free survival (P = 0.016). In vitro, overexpressed FBI-1 significantly enhanced cell migration and invasion both in OVCA 420 and SKOV-3 ovarian carcinoma cells, irrespective of p53 status, accompanied with elevated expression of MT1-MMP, but not MMP-2 or TIMP-2. Moreover, knockdown of MT1-MMP abolished FBI-1-mediated cell migration and invasion. Conversely, stable knockdown of FBI-1 remarkably reduced the motility of these cells with decreased expression of MT1-MMP. Promoter assay and chromatin immunoprecipitation study indicated that FBI-1 could directly interact with the promoter spanning ~600bp of the 5&apos;-flanking sequence of MT1-MMP and enhanced its expression in a dose-dependent manner. Furthermore, stable knockdown and ectopic expression of FBI-1 decreased and increased cell proliferation respectively in OVCA 420, but not in the p53 null SKOV-3 cells.Conclusions: Our results suggested an important role of FBI-1 in ovarian cancer cell proliferation, cell mobility, and invasiveness, and that FBI-1 can be a potential target of chemotherapy. &#169; 2010 Jiang et al; licensee BioMed Central Ltd.</description.abstract>
<language>eng</language>
<publisher>BioMed Central Ltd. The Journal&apos;s web site is located at http://www.molecular-cancer.com</publisher>
<relation.ispartof>Molecular Cancer</relation.ispartof>
<rights>Creative Commons: Attribution 3.0 Hong Kong License</rights>
<rights>Molecular Cancer. Copyright &#169; BioMed Central Ltd.</rights>
<subject.mesh>Cell Line, Tumor</subject.mesh>
<subject.mesh>DNA-Binding Proteins - genetics - metabolism</subject.mesh>
<subject.mesh>Matrix Metalloproteinase 14 - genetics - metabolism</subject.mesh>
<subject.mesh>Ovarian Neoplasms - enzymology - pathology</subject.mesh>
<subject.mesh>Transcription Factors - genetics - metabolism</subject.mesh>
<title>Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers</title>
<type>Article</type>
<description.nature>published_or_final_version</description.nature>
<identifier.doi>10.1186/1476-4598-9-318</identifier.doi>
<identifier.pmid>21176152</identifier.pmid>
<identifier.pmcid>PMC3022670</identifier.pmcid>
<identifier.scopus>eid_2-s2.0-78650278812</identifier.scopus>
<identifier.hkuros>192471</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-78650278812&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>9</identifier.volume>
<identifier.isi>WOS:000286383600001</identifier.isi>
<publisher.place>United Kingdom</publisher.place>
<bitstream.url>http://hub.hku.hk/bitstream/10722/139933/1/1476-4598-9-318.pdf</bitstream.url>
</item>
Author Affiliations
  1. The University of Hong Kong
  2. Imperial College London
  3. University of Texas M. D. Anderson Cancer Center
  4. Sichuan University