Both increased stability and transcription contribute to the induction of the urokinase plasminogen activator receptor (uPAR) message by hypoxia.

Abstract:

:Both hypoxia and overexpression of the urokinase plasminogen activator receptor (uPAR) are associated with a poor clinical outcome in human cancers. Hypoxia has been shown to induce uPAR expression in breast cancer cells and to increase their invasion through Matrigel, a phenomenon which can be blocked using an anti-uPAR antibody. We examined expression of uPAR mRNA in MCF7 human breast carcinoma cells under hypoxia and found that an increase in the level of the message could be detected at 1% oxygen but was most marked at 0.2 or 0.05% oxygen with an induction of 9- to 20-fold over baseline. To determine whether changes in RNA stability contributed to this dramatic increase, we used actinomycin D to inhibit transcription and found that the half-life of the message was much longer under hypoxic conditions (approximately 10 h) than during reoxygenation (approximately 2 h). Transient transfections using a luciferase reporter construct containing 2 kbp of the mouse uPAR promoter showed that promoter activity increased up to 5-fold after exposure to 0.2% oxygen. Thus, hypoxic induction of the uPAR message in MCF7 cells is due to both mRNA stabilization and increased transcriptional activation.

journal_name

Exp Cell Res

authors

Maity A,Solomon D

doi

10.1006/excr.1999.4804

keywords:

subject

Has Abstract

pub_date

2000-03-15 00:00:00

pages

250-7

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(99)94804-8

journal_volume

255

pub_type

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