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Hypoxia Enhances the Expression of Plasminogen Activator Inhibitor-1 in Human Lung Cancer Cells, EBC-1
- Source :
- The Tohoku Journal of Experimental Medicine. 196:259-267
- Publication Year :
- 2002
- Publisher :
- Tohoku University Medical Press, 2002.
-
Abstract
- Plasminogen activator inhibitor-1 (PAI-1) is one of the target genes of hypoxia inducible factor-1alpha (HIF-1alpha). Besides being an important physiological regulator of the fibrinolytic system PAI-1 is also involved in cancer invasiveness. HIF-1alpha is expressed in various types of pulmonary cells, but the relation of PAI-1 to HIF-1alpha under hypoxic condition in these cells are not fully elucidated. We, therefore, studied the effect of hypoxia on the expression of PAI-1 in a lung cancer cell line EBC-1. The expression of HIF-1alpha protein in EBC-1 cells was enhanced by hypoxia, and this was associated with increased secretion of PAI-1. Hypoxia did not affect the levels of HIF-1alpha mRNA but enhanced the PAI-1 mRNA. Pretreatment of the cells with MG132, which inhibits the proteasomal degradation of HIF-1alpha, increased the production of PAI-1 under both normoxia and hypoxia. We conclude that hypoxia induces PAI-1 expression, in EBC-1 cells, through the stabilization of HIF-1 complex and this may be related to cancer metastasis.
- Subjects :
- Lung Neoplasms
Leupeptins
Regulator
Gene Expression
Cysteine Proteinase Inhibitors
General Biochemistry, Genetics and Molecular Biology
chemistry.chemical_compound
Plasminogen Activator Inhibitor 1
MG132
Tumor Cells, Cultured
medicine
Humans
Secretion
Neoplasms, Squamous Cell
G alpha subunit
Messenger RNA
General Medicine
Hypoxia (medical)
Hypoxia-Inducible Factor 1, alpha Subunit
Immunohistochemistry
Molecular biology
Cell Hypoxia
chemistry
Plasminogen activator inhibitor-1
Dactinomycin
Cancer research
medicine.symptom
Plasminogen activator
Transcription Factors
Subjects
Details
- ISSN :
- 13493329 and 00408727
- Volume :
- 196
- Database :
- OpenAIRE
- Journal :
- The Tohoku Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....4693b5fdb9cb54ab0388709915db6b99