GENISTEIN, A TYROSINE KINASE INHIBITOR, REDUCES EGF-INDUCED EGF RECEPTOR INTERNALIZATION AND DEGRADATION IN HUMAN HEPATOMA HEPG2 CELLS

In this work, using the ECL Western blotting assay system, it was foun d that genistein, a specific tyrosine kinase inhibitor, was able to in hibit EGF-induced EGF receptor degradation and tyrosine phosphorylatio n in human hepatoma HepG2 cells. This inhibition was increased with in creasing genistein concentration. With treatment of HepG2 cells with g enistein at 37 degrees C for 30 min, the amount of internalized EGF, w hich was measured by the detection of the sorting of I-125-EGF in the cells, was remarkably decreased. Under the same conditions, in cells u ntreated with genistein, the degradation of EGF was significantly incr eased. After preincubation of HepG2 cells with and without genistein f or 120 min at 37 degrees C, the ratio between degraded and released EG F was 16 and 24, respectively. These results suggest that EGF-induced internalization and degradation of EGF-EGF receptor complexes in HepG2 cells depend on EGF receptor tyrosine kinase activity. (C) 1996 Acade mic Press, Inc.