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Urokinase receptor mRNA level and gene transcription are strongly and rapidly increased by phorbol myristate acetate in human monocyte-like U937 cells

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We have studied the effect of the tumor promotor phorbol myristate acetate (PMA) on the level of mRNA for the receptor for urokinase-type plasminogen activator (u-PAR) in the human monocyte-like cell line U937. PMA causes an early increase in the u-PAR mRNA level which reaches a maximal 50-fold enhancement after 24 h of treatment. Half-maximal stimulation occurs at approximately 5 nM PMA. The effect is observed only with phorbol esters that also act as tumor promotors. The protein synthesis inhibitor cycloheximide (10 micrograms/ml) also increases the level of u-PAR mRNA. Nuclear run-on experiments show a time-dependent increase in the u-PAR gene transcription rate after exposure of the cells to PMA. The PMA-induced increase in u-PAR mRNA is paralleled by a time-dependent increase in u-PAR protein as detected by cross-linking studies with radiolabeled ligand. We conclude that PMA stimulates transcription of the u-PAR gene in U937 cells, and this is responsible at least in part for the accumulation of the u-PAR mRNA and for the subsequent increase in urokinase-binding capacity.

OriginalsprogEngelsk
TidsskriftThe Journal of Biological Chemistry
Vol/bind266
Udgave nummer8
Sider (fra-til)5177-81
Antal sider5
ISSN0021-9258
StatusUdgivet - 15 mar. 1991
Eksternt udgivetJa

ID: 180824157