AACR Meeting Abstracts
HOME HELP FEEDBACK HOW TO CITE ABSTRACTS ARCHIVE CME INFORMATION SEARCH
Cancer ResearchClinical Cancer Research
Cancer Epidemiology Biomarkers & PreventionMolecular Cancer Therapeutics
Molecular Cancer ResearchCancer Prevention Research
Cancer Prevention Journals PortalCancer Reviews Online
Annual Meeting Education BookMeeting Abstracts Online
 QUICK SEARCH:   [advanced]




This Article
Services
Right arrow Similar articles in this journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dubois, C. M.
Right arrow Articles by McMahon, S.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Dubois, C. M.
Right arrow Articles by McMahon, S.
[Proc Amer Assoc Cancer Res, Volume 45, 2004]


Cellular, Molecular, and Tumor Biology 67: Gene Regulation and Tumor Invasion

Abstract #3407

Furin inhibition blocked hypoxia-induced invasion of fibrosarcoma cells. Involvement of HIF-1-induced furin gene expression.

Claire M. Dubois, Sebastien Grandmont and Stephanie McMahon

University of Sherbrooke, Sherbrooke, PQ, Canada

Hypoxia has been recently shown to regulate the in vitro invasion of cancer cells, through the stabilization of the hypoxia-inducible transcription factor HIF-1. Important properties of invasive cancer cells include decreased cell-cell adhesion and increased in ECM remodeling. These events are under the control of key mediators known to be activated by the proprotein convertase furin such as the metalloproteinase MT1-MMP, the integrin E-cadherin and the growth factor TGFbeta. To gain further insights into the mechanism by which hypoxia regulates cell invasion, we tested the impact of furin inhibition on the in vitro invasion of the HT-1080 fibrosarcoma cell line. Stable transfectants were generated using a pcDNA3 vector encoding the furin inhibitor alpha1-PDX or an empty control vector. In control cells, hypoxia (1% O2, 24 h) strongly increased cell invasiveness, an event that correlated with the induction of furin gene expression. Furin inhibition throught alpha1-PDX overexpression, blocked the increased invasiveness of HT-1080 cells due to low oxygen exposition. In luciferase assays, overexpression of the HIF-1 alpha subunit resulted in a marked increased in furin promoter activity, whereas transfection of a dominant negative form of HIF-1alpha impaired hypoxia-induced activity. Similarly, furin promoter activity was increased in the parental Hepa c1c7 cell line but not in the HIF1beta/ARNT-deficient Hepa c4 cells. Together, these results clearly demonstrate the requirement for HIF-1 in the hypoxic regulation of the furin gene and provide additional insights into the mechanism by which hypoxia increases cell invasion.







HOME HELP FEEDBACK HOW TO CITE ABSTRACTS ARCHIVE CME INFORMATION SEARCH
Cancer ResearchClinical Cancer Research
Cancer Epidemiology Biomarkers & PreventionMolecular Cancer Therapeutics
Molecular Cancer ResearchCancer Prevention Research
Cancer Prevention Journals PortalCancer Reviews Online
Annual Meeting Education BookMeeting Abstracts Online
Copyright © 2004 by the American Association for Cancer Research.