Transformation of NIH3T3 fibroblasts by an expression vector for the human epidermal growth factor precursor - PubMed (original) (raw)
Affiliations
- PMID: 2392327
Transformation of NIH3T3 fibroblasts by an expression vector for the human epidermal growth factor precursor
M A Heidaran et al. Oncogene. 1990 Aug.
Abstract
Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) bind to a common cell surface receptor that mediates their diverse biological activities. NIH3T3 fibroblasts transfected with either full-length EGF precursor (preproEGF) or proTGF alpha cDNA displayed distinct patterns of growth in culture. PreproEGF induced focal transformation, and transfectants grew in a chemically defined medium (CDM) at low cell density in the absence of added EGF. In contrast, TGF alpha failed to cause focal transformation, and transfectants grew in CDM in the absence of added growth factors only when seeded at high cell density. The 53 amino acid EGF portion of the preproEGF translation product was essential for its effects. These results indicate that constitutive expression of preproEGF is sufficient to establish autocrine growth of NIH3T3 expressing low levels of EGF receptors. At high cell density, where paracrine as well as autocrine effects of these growth factors would be evident, TGF alpha transfectants displayed at least as high or higher levels of EGF receptor (EGFR) tyrosine phosphorylation than preproEGF transfectants. Since quantitative levels of ligand expression did not account for differences in their transforming properties, preproEGF must be more efficient than proTGF alpha in binding and/or activating EGF receptors in an autocrine manner.
Similar articles
- Transforming growth factor alpha: expression, regulation and biological action of its integral membrane precursor.
Luetteke NC, Lee DC. Luetteke NC, et al. Semin Cancer Biol. 1990 Aug;1(4):265-75. Semin Cancer Biol. 1990. PMID: 2103501 Review. - Inhibition of epidermal growth factor/transforming growth factor-alpha-stimulated cell growth by a synthetic peptide.
Eppstein DA, Marsh YV, Schryver BB, Bertics PJ. Eppstein DA, et al. J Cell Physiol. 1989 Nov;141(2):420-30. doi: 10.1002/jcp.1041410224. J Cell Physiol. 1989. PMID: 2530243 - Tumorigenic transformation of NIH 3T3 cells by the autocrine synthesis of transforming growth factor alpha.
Ju WD, Velu TJ, Vass WC, Papageorge AG, Lowy DR. Ju WD, et al. New Biol. 1991 Apr;3(4):380-8. New Biol. 1991. PMID: 2065023 - Mechanisms by which EGF receptor and TGF alpha contribute to malignant transformation.
Di Marco E, Pierce JH, Aaronson SA, Di Fiore PP. Di Marco E, et al. Nat Immun Cell Growth Regul. 1990;9(3):209-21. Nat Immun Cell Growth Regul. 1990. PMID: 2196461 Review.
Cited by
- Expression cDNA cloning of a transforming gene encoding the wild-type G alpha 12 gene product.
Chan AM, Fleming TP, McGovern ES, Chedid M, Miki T, Aaronson SA. Chan AM, et al. Mol Cell Biol. 1993 Feb;13(2):762-8. doi: 10.1128/mcb.13.2.762-768.1993. Mol Cell Biol. 1993. PMID: 8423800 Free PMC article. - Heparin-binding epidermal growth factor-like growth factor, a v-Jun target gene, induces oncogenic transformation.
Fu Sl, Bottoli I, Goller M, Vogt PK. Fu Sl, et al. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5716-21. doi: 10.1073/pnas.96.10.5716. Proc Natl Acad Sci U S A. 1999. PMID: 10318950 Free PMC article. - Constitutive over-expression of transforming growth factor-alpha in rat liver epithelial cells leads to increased cell cycling without transformation.
Tan TB, Marino PA, Padmanabhan R, Hampton LL, Hanley-Hyde JM, Thorgeirsson SS. Tan TB, et al. In Vitro Cell Dev Biol Anim. 1994 Sep;30A(9):615-21. doi: 10.1007/BF02631261. In Vitro Cell Dev Biol Anim. 1994. PMID: 7820313 - Biological function of PDGF-induced PI-3 kinase activity: its role in alpha PDGF receptor-mediated mitogenic signaling.
Yu JC, Gutkind JS, Mahadevan D, Li W, Meyers KA, Pierce JH, Heidaran MA. Yu JC, et al. J Cell Biol. 1994 Oct;127(2):479-87. doi: 10.1083/jcb.127.2.479. J Cell Biol. 1994. PMID: 7929590 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Research Materials
Miscellaneous