Chromatin binding of epidermal growth factor, nerve growth factor, and platelet-derived growth factor in cells bearing the appropriate surface receptors.

Abstract

We analyzed the uptake and intracellular distribution of 12-5-labeled epidermal growth factor, nerve growth factor, and platelet-derived growth factor in different cell lines that express or do not express the respective surface receptors for these factors. After 1 hr of incubation, all three growth factors were detected in the cytoplasmic fraction and in the nucleus, tightly bound to chromatin. The amount of chromatin-bound growth factors continued to increase during the incubation, and analysis at 48 hr revealed each chromatinbound labeled growth factor in a nondegraded form. After limited digestion of chromatin with DNase 1 (10-20% digested sequences), specific release of all three growth factors was detected only after 1 hr of incubation but not after 24 and 48 hr, suggesting that the DNA regions involved in growth factor binding became nuclease-resistant. Binding of labeled epidermal growth factor and nerve growth factor to isolated chromatin was inhibited by monoclonal antibodies specific for the respective growth factor receptor. The data suggest that chromatin binding may represent an important step in the pathway of growth factor action.The precise mechanism by which different growth factors exert their effects is unclear, although interaction with the appropriate surface receptor and internalization (1-9) are common to all of these factors. The fate of internalized growth factors is controversial. Nerve growth factor (NGF)

Functional growth hormone (GH) receptors and GH are expressed by preimplantation mouse embryos: A role for GH in early embryogenesis?

“…The functional significance of a nuclear GH receptor, while currently unclear, is not without precedent. Other polypeptide hormone receptors have been found to associate with the nucleus, including insulin (27), prolactin (28), epidermal growth factor, nerve growth factor, platelet-derived growth factor (29,30), and fibroblast growth factor (31). That the blastocyst receptor is functional is clearly demonstrated by the actions of GH on cellular functions involving classic early insulin-like effects of GH.…”

Clinical and prognostic significances of nuclear and cytoplasmic KIT expressions in extrahepatic bile duct carcinomas

“…[24][25][26][27][28] In contrast, cytoplasmic KIT expression indicated an increased survival rate in patients with neuroblastoma, hepatocellular carcinoma, and breast cancer. [29][30][31] Several reports described the nuclear translocation of membrane tyrosine kinase receptors, including epidermal growth factor receptor (EGFR), 32 fibroblast growth factor receptor (FGFR), 33 nerve growth factor receptor (NGFR), 34 PDGFR, 35 ErbB-2(HER-2/neu), 36 ErbB-3, 37 and ErbB-4. 38 Nuclear KIT expression was described in several normal tissues and benign and malignant tumors, including normal medullary cells of adrenal glands, pheochromocytomas, 39 sarcomatoid renal cell carcinomas, 40 and GISTs.…”

Hepatoma-derived Growth Factor Is a Neurotrophic Factor Harbored in the Nucleus

“…Although we have not examined the turnover of HDGF in vivo, these protein movements might be finely controlled under physiological conditions. Some growth factors including nerve growth factor, epidermal growth factor, and platelet-derived growth factor, have been reported to exert their effects by binding to their receptor, being internalized, and being conveyed to the nucleus associated with their receptor or even without a receptor by targeting to the nucleus (37)(38)(39). Exogenously supplied HDGF is reported to induce proliferation of fibroblasts (1), endothelial cells (10), vascular smooth muscle cells (11), and some hepatoma cells (12).…”