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Inhibition of epidermal growth factor receptor activity by retinoic acid in glioma cells
Author(s) -
Steck Peter A.,
Hadi Azra,
Lotan Reuben,
Yung W. K. Alfred
Publication year - 1990
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240420204
Subject(s) - epidermal growth factor receptor , retinoic acid , glioma , retinoic acid receptor , chemistry , cancer research , epidermal growth factor , receptor , microbiology and biotechnology , biology , biochemistry , gene
Abstract The growth inhibitory effects of exogenously added retinoic acid (RA) on various cultured human glioma cells was observed to be heterogenous, with an ID 50 ranging from 10 −7 M to no response. The protein tyrosine kinase activity of epidermal growth factor receptor (EGF‐receptor) appeared to parallel the cell's growth responsiveness to RA. Cells sensitive to RA‐induced growth inhibition exhibited a dose‐dependent decrease in EGF‐receptor activity, whereas RA‐resistant cells showed no alterations in EGF‐receptor protein tyrosine kinase activity or expression. The modulation of EGF‐receptor by RA was further examined with RA‐sensitive (LG) and ‐resistant (NG‐1 ) cell lines. Both cell lines were approximately equal in their ability to bind and internalize epidermal growth factor in the presence or absence of RA. Several independent assays suggested that the inhibition of EGF‐receptor activity was independent of protein kinase C modulation as mediated by phorbol myristate acetate. However, alterations in associated glycoconjugates of EGF‐receptor were observed among the sensitive cells but not the resistant cells. These results suggest RA‐induced growth inhibition in sensitive cells may arise, at least in part, through alterations in EGF‐receptor activity and structure.