Abstract
Cultured rat pituitary tumor cells, GH3/D6, which synthesize both growth hormone and prolactin, have cell-surface epidermal growth factor (EGF) receptor sites (34,000 per cell) that bind 125I-labeled EGF with a high affinity (Kd approximately 1 nM). Prolonged treatment of the cells with EGF did not stimulate cell division but did inhibit thyroid hormone-stimulated cell growth. In addition, EGF altered the morphology of the cells from a rounded to an elongated conformation. EGF also induced a perturbation of chromatin structure in GH3 cell nuclei that was detected by an increase (40%) in the number of rifampicin-resistant initiation sites for bacterial RNA polymerase. This was accompanied by an increased synthesis of prolactin and an inhibition of synthesis of growth hormone. In the presence of EGF, the synthesis of growth hormone was no longer inducible by thyroid hormone, but it remained responsive to glucocorticoids. The results demonstrate that EGF can elicit major effects on the cellular phenotype and expression of specific genes in the absence of a proliferative response. This suggests that EGF can also regulate differentiated cellular functions.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Carpenter G., Cohen S. 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts. J Cell Biol. 1976 Oct;71(1):159–171. doi: 10.1083/jcb.71.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen L. B., Gallimore P. H., McDougall J. K. Correlation between tumor induction and the large external transformation sensitive protein on the cell surface. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3570–3574. doi: 10.1073/pnas.73.10.3570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen L. B., Gudor R. C., Sun T. T., Chen A. B., Mosesson M. W. Control of a cell surface major glycoprotein by epidermal growth factor. Science. 1977 Aug 19;197(4305):776–778. doi: 10.1126/science.302030. [DOI] [PubMed] [Google Scholar]
- Cohen S., Savage C. R., Jr Recent studies on the chemistry and biology of epidermal growth factor. Recent Prog Horm Res. 1974;30(0):551–574. doi: 10.1016/b978-0-12-571130-2.50018-3. [DOI] [PubMed] [Google Scholar]
- Cohen S., Taylor J. M. Epidermal growth factor: chemical and biological characterization. Recent Prog Horm Res. 1974;30(0):533–550. doi: 10.1016/b978-0-12-571130-2.50017-1. [DOI] [PubMed] [Google Scholar]
- Dannies P. S., Tashjian A. R., Jr Effects of thyrotropin-releasing hormone and hydrocortisone on synthesis and degradation of prolactin in a rat pituitary cell strain. J Biol Chem. 1973 Sep 10;248(17):6174–6179. [PubMed] [Google Scholar]
- Engvall E., Ruoslahti E. Binding of soluble form of fibroblast surface protein, fibronectin, to collagen. Int J Cancer. 1977 Jul 15;20(1):1–5. doi: 10.1002/ijc.2910200102. [DOI] [PubMed] [Google Scholar]
- Evans G. A., David D. N., Rosenfeld M. G. Regulation of prolactin and somatotropin mRNAs by thyroliberin. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1294–1298. doi: 10.1073/pnas.75.3.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gospodarowicz D., Ill C. R., Birdwell C. R. Effects of fibroblast and epidermal growth factors on ovarian cell proliferation in vitro. I. Characterization of the response of granulosa cells to FGF and EGF. Endocrinology. 1977 Apr;100(4):1108–1120. doi: 10.1210/endo-100-4-1108. [DOI] [PubMed] [Google Scholar]
- Haigler H. T., McKanna J. A., Cohen S. Direct visualization of the binding and internalization of a ferritin conjugate of epidermal growth factor in human carcinoma cells A-431. J Cell Biol. 1979 May;81(2):382–395. doi: 10.1083/jcb.81.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson L. K., Baxter J. D. Regulation of gene expression by glucocorticoid hormones. Early effects preserved in isolated chromatin. J Biol Chem. 1978 Mar 25;253(6):1991–1997. [PubMed] [Google Scholar]
- Johnson L. K., Lan N. C., Baxter J. D. Stimulation and inhibition of cellular functions by glucocorticoids. Correlations with rapid influences on chromatin structure. J Biol Chem. 1979 Aug 25;254(16):7785–7794. [PubMed] [Google Scholar]
- Martial J. A., Seeburg P. H., Guenzi D., Goodman H. M., Baxter J. D. Regulation of growth hormone gene expression: synergistic effects of thyroid and glucocorticoid hormones. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4293–4295. doi: 10.1073/pnas.74.10.4293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
- O'Farrell P. Z., Goodman H. M., O'Farrell P. H. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977 Dec;12(4):1133–1141. doi: 10.1016/0092-8674(77)90176-3. [DOI] [PubMed] [Google Scholar]
- Rheinwald J. G., Green H. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature. 1977 Feb 3;265(5593):421–424. doi: 10.1038/265421a0. [DOI] [PubMed] [Google Scholar]
- Rubin C. S., Rosen O. M. Protein phosphorylation. Annu Rev Biochem. 1975;44:831–887. doi: 10.1146/annurev.bi.44.070175.004151. [DOI] [PubMed] [Google Scholar]
- Savage C. R., Jr, Cohen S. Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization. J Biol Chem. 1972 Dec 10;247(23):7609–7611. [PubMed] [Google Scholar]
- Schlessinger J., Shechter Y., Willingham M. C., Pastan I. Direct visualization of binding, aggregation, and internalization of insulin and epidermal growth factor on living fibroblastic cells. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2659–2663. doi: 10.1073/pnas.75.6.2659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sun T. T., Green H. Cultured epithelial cells of cornea, conjunctiva and skin: absence of marked intrinsic divergence of their differentiated states. Nature. 1977 Oct 6;269(5628):489–493. doi: 10.1038/269489a0. [DOI] [PubMed] [Google Scholar]
- Vlodavsky I., Brown K. D., Gospodarowicz D. A comparison of the binding of epidermal growth factor to cultured granulosa and luteal cells. J Biol Chem. 1978 May 25;253(10):3744–3750. [PubMed] [Google Scholar]
- Vlodavsky I., Johnson L. K., Gospodarowicz D. Appearance in confluent vascular endothelial cell monolayers of a specific cell surface protein (CSP-60) not detected in actively growing endothelial cells or in cell types growing in multiple layers. Proc Natl Acad Sci U S A. 1979 May;76(5):2306–2310. doi: 10.1073/pnas.76.5.2306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wartiovaara J., Linder E., Ruoslahti E., Vaheri A. Distribution of fibroblast surface antigen: association with fibrillar structures of normal cells and loss upon viral transformation. J Exp Med. 1974 Dec 1;140(6):1522–1533. doi: 10.1084/jem.140.6.1522. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wibo M., Poole B. Protein degradation in cultured cells. II. The uptake of chloroquine by rat fibroblasts and the inhibition of cellular protein degradation and cathepsin B1. J Cell Biol. 1974 Nov;63(2 Pt 1):430–440. doi: 10.1083/jcb.63.2.430. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamada K. M., Yamada S. S., Pastan I. Cell surface protein partially restores morphology, adhesiveness, and contact inhibition of movement to transformed fibroblasts. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1217–1221. doi: 10.1073/pnas.73.4.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]



