Tohoku J. Exp. Med., 2002, 196 (4)

Hypoxia Enhances the Expression of Plasminogen Activator Inhibitor-1
in Human Lung Cancer Cells, EBC-1

DAISUKE KIMURA, TADAATSU IMAIZUMI,¹ WAKAKO TAMO,¹ TAKEHIRO SAKAI,
KAZUO ITO, RYO HATANAKA, HIDEMI YOSHIDA,¹ TAKAO TSUSHIMA,
KEI SATOH¹ and IKUO FUKUDA

The First Department of Surgery, and ¹Department of Vascular Biology, Institute of Brain Science,
Hirosaki University School of Medicine, Hirosaki 036-8562

Plasminogen activator inhibitor-1 (PAI-1) is one of the target genes of hypoxia inducible factor-1a (HIF-1a). Besides being an important physiological regulator of the fibrinolytic system PAI-1 is also involved in cancer invasiveness. HIF-1a is expressed in various types of pulmonary cells, but the relation of PAI-1 to HIF-1a 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-1a 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-1a mRNA but enhanced the PAI-1 mRNA. Pretreatment of the cells with MG132, which inhibits the proteasomal degradation of HIF-1a, 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.

Keywords—— hypoxia; plasminogen activator inhibitor-1; hypoxia inducible factor-1a; lung cancer cell; MG132

© 2002 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2002, 196, 259-267

Address for reprints: Daisuke Kimura, The First Department of Surgery, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.

e-mail: dkimura@cc.hirosaki-u.ac.jp