Abstract
Multidrug-resistant sublines of Chinese hamster lung and mouse tumor cells selected for high levels of resistance to vincristine or actinomycin D have increased numbers of epidermal growth factor (EGF) receptors compared to control cells. Evidence for this increase was found in six of six resistant cell lines with the use of receptor binding or immunoprecipitation techniques. Levels of 125I-labeled EGF binding to intact actinomycin D-resistant cells derived from DC-3F or CLM-7 Chinese hamster lines are increased 3- to 10-fold compared to controls. Scatchard analysis of these data suggests that increased binding is a result of increased receptor number rather than altered affinity of receptor for ligand. Affinity-labeling and immunoprecipitation studies confirmed the finding of increased receptor amount in resistant hamster and mouse cells. Multidrug-resistant variants of DC-3F cells overproduce a plasma membrane glycoprotein (gp150-180) with several physicochemical properties that resemble those of EGF receptor. However, electrophoretic transfer blots with a polyclonal antibody to gp150-180 show that EGF receptor and gp150-180 are probably different molecules. Resistant cells described in this report manifest a normalized phenotype compared to transformed, tumorigenic, drug-sensitive parental cells. EGF receptor increase in resistant variants may be associated with this reverse transformation.
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.
- Beck W. T., Mueller T. J., Tanzer L. R. Altered surface membrane glycoproteins in Vinca alkaloid-resistant human leukemic lymphoblasts. Cancer Res. 1979 Jun;39(6 Pt 1):2070–2076. [PubMed] [Google Scholar]
- Biedler J. L., Chang T. D., Meyers M. B., Peterson R. H., Spengler B. A. Drug resistance in Chinese hamster lung and mouse tumor cells. Cancer Treat Rep. 1983 Oct;67(10):859–867. [PubMed] [Google Scholar]
- Biedler J. L., Riehm H. Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross-resistance, radioautographic, and cytogenetic studies. Cancer Res. 1970 Apr;30(4):1174–1184. [PubMed] [Google Scholar]
- Biedler J. L., Riehm H., Peterson R. H., Spengler B. A. Membrane-mediated drug resistance and phenotypic reversion to normal growth behavior of Chinese hamster cells. J Natl Cancer Inst. 1975 Sep;55(3):671–680. doi: 10.1093/jnci/55.3.671. [DOI] [PubMed] [Google Scholar]
- COHEN S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem. 1962 May;237:1555–1562. [PubMed] [Google Scholar]
- Carlin C. R., Knowles B. B. Biosynthesis of the epidermal growth factor receptor in human epidermoid carcinoma-derived A431 cells. J Biol Chem. 1984 Jun 25;259(12):7902–7908. [PubMed] [Google Scholar]
- Carlin C. R., Phillips P. D., Knowles B. B., Cristofalo V. J. Diminished in vitro tyrosine kinase activity of the EGF receptor of senescent human fibroblasts. Nature. 1983 Dec 8;306(5943):617–620. doi: 10.1038/306617a0. [DOI] [PubMed] [Google Scholar]
- Carpenter G., Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216. doi: 10.1146/annurev.bi.48.070179.001205. [DOI] [PubMed] [Google Scholar]
- Carpenter G., Lembach K. J., Morrison M. M., Cohen S. Characterization of the binding of 125-I-labeled epidermal growth factor to human fibroblasts. J Biol Chem. 1975 Jun 10;250(11):4297–4304. [PubMed] [Google Scholar]
- Cohen S., Fava R. A., Sawyer S. T. Purification and characterization of epidermal growth factor receptor/protein kinase from normal mouse liver. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6237–6241. doi: 10.1073/pnas.79.20.6237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen S., Ushiro H., Stoscheck C., Chinkers M. A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles. J Biol Chem. 1982 Feb 10;257(3):1523–1531. [PubMed] [Google Scholar]
- Das M., Miyakawa T., Fox C. F., Pruss R. M., Aharonov A., Herschman H. R. Specific radiolabeling of a cell surface receptor for epidermal growth factor. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2790–2794. doi: 10.1073/pnas.74.7.2790. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
- GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garman D., Center M. S. Alterations in cell surface membranes in Chinese hamster lung cell resistant to adriamycin. Biochem Biophys Res Commun. 1982 Mar 15;105(1):157–163. doi: 10.1016/s0006-291x(82)80025-9. [DOI] [PubMed] [Google Scholar]
- Gospodarowicz D., Moran J. S. Growth factors in mammalian cell culture. Annu Rev Biochem. 1976;45:531–558. doi: 10.1146/annurev.bi.45.070176.002531. [DOI] [PubMed] [Google Scholar]
- Jetten A. M. Action of retinoids and phorbol esters on cell growth and the binding of epidermal growth factor. Ann N Y Acad Sci. 1981 Feb 27;359:200–217. doi: 10.1111/j.1749-6632.1981.tb12748.x. [DOI] [PubMed] [Google Scholar]
- Juliano R. Drug-resistant mutants of Chinese hamster ovary cells possess an altered cell surface carbohydrate component. J Supramol Struct. 1976;4(4):521–526. doi: 10.1002/jss.400040412. [DOI] [PubMed] [Google Scholar]
- King L. E., Jr, Carpenter G., Cohen S. Characterization by electrophoresis of epidermal growth factor stimulated phosphorylation using A-431 membranes. Biochemistry. 1980 Apr 1;19(7):1524–1528. doi: 10.1021/bi00548a040. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lesniak M. A., Roth J., Gorden P., Gavin J. R., 3rd Human growth hormone radioreceptor assay using cultured human lymphocytes. Nat New Biol. 1973 Jan 3;241(105):20–22. doi: 10.1038/newbio241020a0. [DOI] [PubMed] [Google Scholar]
- Meyers M. B., Biedler J. L. Increased synthesis of a low molecular weight protein in vincristine-resistant cells. Biochem Biophys Res Commun. 1981 Mar 16;99(1):228–235. doi: 10.1016/0006-291x(81)91736-8. [DOI] [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]
- Peterson R. H., Biedler J. L. Plasma membrane proteins and glycoproteins from Chinese hamster cells sensitive and resistant to actinomycin D. J Supramol Struct. 1978;9(3):289–298. doi: 10.1002/jss.400090302. [DOI] [PubMed] [Google Scholar]
- Peterson R. H., Meyers M. B., Spengler B. A., Biedler J. L. Alteration of plasma membrane glycopeptides and gangliosides of Chinese hamster cells accompanying development of resistance to daunorubicin and vincristine. Cancer Res. 1983 Jan;43(1):222–228. [PubMed] [Google Scholar]
- Peterson R. H., O'Neil J. A., Biedler J. L. Some biochemical properties of Chinese hamster cells sensitive and resistant to actinomycin D. J Cell Biol. 1974 Dec;63(3):773–779. doi: 10.1083/jcb.63.3.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riehm H., Biedler J. L. Cellular resistance to daunomycin in Chinese hamster cells in vitro. Cancer Res. 1971 Apr;31(4):409–412. [PubMed] [Google Scholar]
- Riordan J. R., Deuchars K., Kartner N., Alon N., Trent J., Ling V. Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. 1985 Aug 29-Sep 4Nature. 316(6031):817–819. doi: 10.1038/316817a0. [DOI] [PubMed] [Google Scholar]
- Ross R. A., Spengler B. A., Biedler J. L. Coordinate morphological and biochemical interconversion of human neuroblastoma cells. J Natl Cancer Inst. 1983 Oct;71(4):741–747. [PubMed] [Google Scholar]
- Schaudies R. P., Harper R. A., Savage C. R., Jr 125I-EGF binding to responsive and nonresponsive cells in culture: loss of cell-associated radioactivity relates to growth induction. J Cell Physiol. 1985 Sep;124(3):493–498. doi: 10.1002/jcp.1041240320. [DOI] [PubMed] [Google Scholar]
- Stoscheck C. M., King L. E., Jr Role of epidermal growth factor in carcinogenesis. Cancer Res. 1986 Mar;46(3):1030–1037. [PubMed] [Google Scholar]
- Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wakshull E., Kraemer P. M., Wharton W. Multistep change in epidermal growth factor receptors during spontaneous neoplastic progression in Chinese hamster embryo fibroblasts. Cancer Res. 1985 May;45(5):2070–2075. [PubMed] [Google Scholar]
- Winter W. P., Yodh J. Interaction of human hemoglobin and its variants with agar. Science. 1983 Jul 8;221(4606):175–178. doi: 10.1126/science.6190229. [DOI] [PubMed] [Google Scholar]