Title of article :
Mechanism of novel vitamin K analog induced growth inhibition in human hepatoma cell line
Author/Authors :
Shinji Osada، نويسنده , , Brian I. Carr، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2001
Pages :
7
From page :
676
To page :
682
Abstract :
Background/Aims: To understand the mechanisms of liver regeneration or hepatoma apoptosis, it is important to estimate the turning point of the signal transduction by growth factor receptor. Since 2-(2-hydroxyethylsulfaryl) 3-methyl-1,4-naphthoquinone or CPD 5 has been shown to mediate the phosphorylation of epidermal growth factor (EGF) receptor in Hep3B hepatoma cells, the differences between EGF and CPD 5-mediated signal transduction were studied. Methods: DNA content was measured by Hoechst fluorescent assay. Phosphorylated proteins were described with Western blots or two-dimensional electrophoresis. Results: CPD 5-induced EGFR phosphorylation was functional to stimulate Ras pathway. However, CPD 5-mediated extracellular signal-regulated kinase (ERK) phosphorylation was not antagonized by inhibition of upstream activation with PD153035. CPD 5 inhibited ERK dephosphorylation in cell lysate, suggesting that ERK phosphorylation by CPD 5 was depending on kinase activity and phosphatase inhibition. Two-dimensional electrophoresis showed extra phospho ERK spot, which was indicated to have close association with CPD 5-induced growth inhibition, since U0126 antagonized growth inhibition and appearance of this spot. Conclusions: The turning point of EGFR pathway was proved to have close association with the expressed level of phosphorylated ERK. ERK phosphorylation was suggested to play a critical role in growth factor-induced signal transduction.
Keywords :
Vitamin K analog , hepatoma cells , Extracellular signal-related kinase , epidermal growth factor , phosphorylation
Journal title :
Journal of Hepatology
Serial Year :
2001
Journal title :
Journal of Hepatology
Record number :
585232
Link To Document :
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