Studies on the mechanism by which a tumor promoter inhibits binding of epidermal growth factor to cellular receptors.

Abstract:

:This study analyzes the mechanism by which the tumor promoter 12-0-tetradecanoyl-phorbol 13-acetate (TPA) inhibits binding of epidermal growth factor (EGF) to its membrane receptors in HeLa cells. Kinetic studies indicate that inhibition of EGF binding occurs within a few minutes after exposure of cells to TPA; delayed addition of TPA causes a reduction in previously bound EGF. With prolonged exposure to TPA, the cells become refractory to TPA inhibition of EGF binding. Evidence was obtained that TPA acts by causing the dissociation of EGF-receptor complexes present on the cell surface and not by increasing the proteolytic degradation or internalization of EGF. Evidence that the TPA inhibition of EGF-receptor binding is not a direct consequence of TPA binding to the "active site" of EGF receptors was obtained by the differential effects of pH, temperature or exposure time and that TPA does not inhibit EGF binding when added to isolated plasma membrane fragments. Studies with a variety of inhibitors suggest that the TPA inhibition of EGF-receptor binding does not require macromolecular synthesis, energy metabolism, or cytoskeletal changes. Taken together, our results suggest that TPA inhibition of EGF-receptor binding results from TPA-induced changes in the membrane microenvironment of EGF receptors.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Lee LS,Weinstein IB

doi

10.1093/carcin/1.8.669

keywords:

subject

Has Abstract

pub_date

1980-08-01 00:00:00

pages

669-79

issue

8

eissn

0143-3334

issn

1460-2180

journal_volume

1

pub_type

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