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Article: Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers

TitleOverexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers
Authors
Issue Date2010
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.com
Citation
Molecular Cancer, 2010, v. 9 How to Cite?
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'-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.
Persistent Identifierhttp://hdl.handle.net/10722/139933
ISSN
2013 Impact Factor: 5.397
2013 SCImago Journal Rankings: 2.876
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorJiang, Len_HK
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorWong, OGWen_HK
dc.contributor.authorTam, KFen_HK
dc.contributor.authorLam, EWFen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorLe, XFen_HK
dc.contributor.authorWong, ESYen_HK
dc.contributor.authorChan, HYen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2011-09-23T06:01:56Z-
dc.date.available2011-09-23T06:01:56Z-
dc.date.issued2010en_HK
dc.identifier.citationMolecular Cancer, 2010, v. 9en_HK
dc.identifier.issn1476-4598en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139933-
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.en_HK
dc.languageengen_US
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.molecular-cancer.comen_HK
dc.relation.ispartofMolecular Canceren_HK
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 cancersen_HK
dc.typeArticleen_HK
dc.identifier.emailSiu, MKY: mkysiu@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.authoritySiu, MKY=rp00275en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1476-4598-9-318en_HK
dc.identifier.pmid21176152-
dc.identifier.pmcidPMC3022670-
dc.identifier.scopuseid_2-s2.0-78650278812en_HK
dc.identifier.hkuros192471en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78650278812&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume9en_HK
dc.identifier.isiWOS:000286383600001-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridJiang, L=36801738800en_HK
dc.identifier.scopusauthoridSiu, MKY=24924018400en_HK
dc.identifier.scopusauthoridWong, OGW=7004813981en_HK
dc.identifier.scopusauthoridTam, KF=35622901400en_HK
dc.identifier.scopusauthoridLam, EWF=7102889877en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridLe, XF=16637748300en_HK
dc.identifier.scopusauthoridWong, ESY=23101622300en_HK
dc.identifier.scopusauthoridChan, HY=26024081600en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK

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