Rakowicz-Szulczynska E M, Otwiaska D, Rodeck U, Koprowski H
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Arch Biochem Biophys. 1989 Feb 1;268(2):456-64. doi: 10.1016/0003-9861(89)90313-5.
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.
在表达表皮生长因子（EGF）表面受体的细胞系中，分析了表皮生长因子（EGF）、针对EGF表面受体蛋白结构域的单克隆抗体（MAb 425）以及针对EGF受体上碳水化合物Y决定簇的单克隆抗体（MAb Br 15 - 6A）的细胞摄取、核转位及与染色质的结合情况。EGF和MAb 425均转位至细胞核，并以未降解的形式结合到所有受试细胞的染色质上。MAb Br 15 - 6A仅被表达EGF受体的SW 948结肠癌细胞摄取，而不表达EGF受体的SW 707结肠癌细胞既不摄取EGF也不摄取MAb 425。MAb 425免疫沉淀出一种230至250 kDa的染色质蛋白，该蛋白似乎是EGF染色质受体。EGF定位于单个EcoRI DNA片段，这表明染色质结合具有高度特异性。EGF与主要对DNase II敏感的染色质区域的结合保护了这些区域免受核酸酶作用。文中讨论了生长因子与染色质结合在肿瘤转化中的作用。
