Requirement for epidermal growth factor receptor tyrosine kinase and for 12-lipoxygenase activity in the expression of 12-lipoxygenase in human epidermoid carcinoma cells

Biochemical Pharmacology
W Hagmann, S Borgers

Abstract

We studied the dependency of basal 12-lipoxygenase (12-LOX; arachidonate:oxygen 12-oxidoreductase, EC 1.13.11.31) expression and activity on functional protein tyrosine kinase of the epidermal growth factor receptor (EGF-R) and on 12-LOX activity in human A431 epidermoid carcinoma cells. Treatment of cells with inhibitors of high specificity for EGF-R tyrosine kinase, namely PD 153035 and 4,5-dianilinophthalimide (DAPH1), decreased cellular 12-LOX at mRNA, protein, and activity levels in a time- and dose-dependent manner, with PD 153035 being effective at concentrations below 1 microM. After 24-hr incubation with 10 microM PD 153035 or DAPH1, 12-LOX activity dropped to 14% (39%), and 12-LOX protein to 25% (24%) of control level. Inhibition of 12-LOX activity by the compound N-benzyl-N-hydroxy-5-phenylpentanamide (BHPP) also resulted in a substantial decrease in 12-LOX protein expression. 12-LOX mRNA levels were diminished or undetectable by reverse transcription-polymerase chain reaction after cell treatment with these inhibitors. Our results suggest that basal 12-LOX expression in A431 tumor cells largely depends on functional EGF-R tyrosine kinase, and that 12-LOX activity is required in the EGF-elicited intracellular signali...Continue Reading

References

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Citations

Jan 1, 1997·Pathology Oncology Research : POR·Wolfgang Hagmann
Apr 17, 2003·Experimental Eye Research·Paulo OttinoHaydee E P Bazan
Nov 16, 2002·Prostaglandins & Other Lipid Mediators·Tanihiro Yoshimoto, Yoshitaka Takahashi
Nov 4, 2000·Expert Opinion on Investigational Drugs·V E SteeleG J Kelloff
Aug 30, 2002·Biochemical and Biophysical Research Communications·Wei-Gang TongThomas E Adrian
May 15, 2013·Chemical Biology & Drug Design·Carolina MascayanoSteve Perry

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