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HeLa cell mutants resistant to epidermal growth factor ricin A‐chain conjugate
Author(s) -
Banker Deborah,
Herschman Harvey R.
Publication year - 1989
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041390108
Subject(s) - epidermal growth factor , heparin binding egf like growth factor , hela , diphtheria toxin , mutant , endosome , ricin , cell culture , microbiology and biotechnology , lysosome , biology , intracellular , receptor , chemistry , biochemistry , cell , toxin , genetics , gene , enzyme
Abstract Epidermal growth factor (EGF) was linked to the toxic A chain of ricin toxin (RTA) to produce an EGF‐receptor‐specific cytotoxic agent, EGF‐RTA. Three EGF‐RTA‐resistant mutants of the human HeLa cell line were selected. These mutant cell lines are 10‐fold to more than 100‐fold more resistant to EGF‐RTA when compared to HeLa cells. The EGF‐RTA‐resistant mutants have at least as many EGF receptors as parent cells; the basis for the EGF‐RTA‐resistant phenotype must be distal to EGF binding. The EGF‐RTA‐resistant cells are not cross‐resistant to ricin or to diphtheria toxin; their mutant phenotype appears to be EGF specific. The EGF‐RTA‐resistant mutants are able to internalize and degrade EGF. However, the mutants have altered EGF receptor down‐regulation and phorbol 12‐tetradecanoate 13‐acetate modulation properties. EGF‐RTA/ammonium chloride and EGF‐RTA/adenovirus co‐treatment data suggest that the mutant defect(s) which confers EGF‐RTA resistance is either in the endosome or at a step(s) in the intracellular EGF processing pathway between the endosome and the lysosome.