Enhanced Tumorigenesis of NR6 Cells Which Express Non-Down-Regulating Epidermal Growth Factor Receptors
作者： Cheri S. Lazar , Alan Wells , Gordon N. Gill , Hideo Masui , Michael G. Rosenfeld
DOI:
关键词:
摘要: Sequences in the regulatory carboxyl terminus of epidermal growth factor (EGF) receptor are required for ligand-induced internalization via a high-affinity saturable endocytic pathway and down-regulation. To investigate role down-regulation attenuating mitogenic signals, we compared ability NR6 cells expressing holo mutant defective EGF receptors to form tumors athymic mice. reproducibly formed rapidly growing tumors, whereas had low tumorigenic potential. Serial passage resulted an enhanced rate tumor formation that directly correlated with increased expression receptors. Tumor was inhibited by competitive antagonist anti-EGF monoclonal antibody. Excessive signaling from cell surface can result lack sequences endocytosis saturation mechanisms. Non-down-regulating kinase-active provide especially strong signal, manifested as rapid
aacrjournals.org参考文章(22)
L.K. Opresko, K.A. Lund, C. Starbuck, B.J. Walsh, H.S. Wiley, Quantitative analysis of the endocytic system involved in hormone-induced receptor internalization. Journal of Biological Chemistry. ,vol. 265, pp. 15713- 15723 ,(1990) , 10.1016/S0021-9258(18)55456-9
T Kawamoto, J Mendelsohn, A Le, G H Sato, C S Lazar, G N Gill, Relation of epidermal growth factor receptor concentration to growth of human epidermoid carcinoma A431 cells. Journal of Biological Chemistry. ,vol. 259, pp. 7761- 7766 ,(1984) , 10.1016/S0021-9258(17)42858-4
T J Velu, W C Vass, D R Lowy, L Beguinot, Functional heterogeneity of proto-oncogene tyrosine kinases: the C terminus of the human epidermal growth factor receptor facilitates cell proliferation. Molecular and Cellular Biology. ,vol. 9, pp. 1772- 1778 ,(1989) , 10.1128/MCB.9.4.1772
William S. Chen, Cheri S. Lazar, Kirk A. Lund, John B. Welsh, Chia-Ping Chang, Gordon M. Walton, Channing J. Der, H.Steven Wiley, Gordon N. Gill, Michael G. Rosenfeld, Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation. Cell. ,vol. 59, pp. 33- 43 ,(1989) , 10.1016/0092-8674(89)90867-2
Towia A. Libermann, Harris R. Nusbaum, Nissim Razon, Richard Kris, Irit Lax, Hermona Soreq, Nigel Whittle, Michael D. Waterfield, Axel Ullrich, Joseph Schlessinger, Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin Nature. ,vol. 313, pp. 144- 147 ,(1985) , 10.1038/313144A0
R. N. Fabricant, J. E. De Larco, G. J. Todaro, Nerve growth factor receptors on human melanoma cells in culture Proceedings of the National Academy of Sciences of the United States of America. ,vol. 74, pp. 565- 569 ,(1977) , 10.1073/PNAS.74.2.565
J B Welsh, G N Gill, M G Rosenfeld, A Wells, A negative feedback loop attenuates EGF-induced morphological changes. Journal of Cell Biology. ,vol. 114, pp. 533- 543 ,(1991) , 10.1083/JCB.114.3.533
Clifford J. Tabin, Scott M. Bradley, Cornelia I. Bargmann, Robert A. Weinberg, Alex G. Papageorge, Edward M. Scolnick, Ravi Dhar, Douglas R. Lowy, Esther H. Chang, Mechanism of activation of a human oncogene. Nature. ,vol. 300, pp. 143- 149 ,(1982) , 10.1038/300143A0
J. Downward, Y. Yarden, E. Mayes, G. Scrace, N. Totty, P. Stockwell, A. Ullrich, J. Schlessinger, M. D. Waterfield, Close similarity of epidermal growth factor receptor and v- erb-B oncogene protein sequences Nature. ,vol. 307, pp. 521- 527 ,(1984) , 10.1038/307521A0
DavidE. Neal, MarkK. Bennett, ReginaldR. Hall, Colin Marsh, PaulD. Abel, J.R.C. Sainsbury, AdrianL. Harris, Epidermal-growth-factor receptors in human bladder cancer: comparison of invasive and superficial tumours. The Lancet. ,vol. 325, pp. 366- 368 ,(1985) , 10.1016/S0140-6736(85)91386-8