Hypoxia enhances the expression of plasminogen activator inhibitor-1 in human lung cancer cells, EBC-1.
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.
Kimura
Daisuke
D
The First Department of Surgery, Institute of Brain Science, Hirosaki University School of Medicine, Japan. dkimura@cc.hirosaki-u.ac.jp
Imaizumi
Tadaatsu
T
Tamo
Wakako
W
Sakai
Takehiro
T
Ito
Kazuo
K
Hatanaka
Ryo
R
Yoshida
Hidemi
H
Tsushima
Takao
T
Satoh
Kei
K
Fukuda
Ikuo
I
D015687:Cell Hypoxia; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D007976:Leupeptins / Q000494:pharmacology; D008175:Lung Neoplasms; D018307:Neoplasms, Squamous Cell; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D015853:Cysteine Proteinase Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007976:Leupeptins; D017395:Plasminogen Activator Inhibitor 1; D014157:Transcription Factors; D003609:Dactinomycin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde