Epidermal growth factor (EGF) and monoclonal antibody to cell surface EGF receptor bind to the same chromatin receptor.
Cellular uptake, nuclear translocation, and chromatin binding of epidermal growth factor (EGF) and monoclonal antibodies (MAbs) against the protein domain of the EGF surface receptor (MAb 425) and against the carbohydrate Y determinant on the EGF receptor (MAb Br 15-6A) were analyzed in cell lines that express surface EGF receptor. Both EGF and MAb 425 were translocated to the nucleus and bound in nondegraded form to the chromatin of all cells tested. MAb Br 15-6A was taken up only by SW 948 colorectal carcinoma cells which express EGF receptor whereas neither EGF nor MAb 425 was taken up by SW 707 colorectal carcinoma cells which do not express EGF receptor. MAb 425 immunoprecipitated a 230- to 250-kDa chromatin protein, which appears to be the EGF chromatin receptor. EGF was localized in a single EcoRI DNA fragment suggesting that the chromatin binding was highly specific. Binding of EGF to primarily DNase II-sensitive chromatin regions protected these regions from nuclease action. The role of growth factor binding to chromatin in neoplastic transformation is discussed.
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
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Rakowicz-Szulczynska
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Otwiaska
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Rodeck
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Koprowski
D000911:Antibodies, Monoclonal / Q000276:immunology; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002843:Chromatin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II