Production of Erythropoietin by an Established Human Renal Carcinoma Cell Line: In Vitro and In Vivo Studies

  • Daniel Shouval
  • Judith B. Sherwood
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 34)


The inverse relationship between tissue oxygenation and circulating erythropoietin levels has been well documented in clinical and in vivo experimental studies1. Although a considerable body of information exists on the correlation between erythropoietin production in vivo and such parameters involved in oxygen supply as hemoglobin concentration, red cell mass, ambient pO2, and hemoglobin-oxygen affinity, little information exists on regulation of erythropoietin synthesis and secretion at the cellular level.


Nude Mouse Athymic Mouse Human Renal Carcinoma Cell Erythropoietin Level Erythropoietin Production 
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  1. 1.
    Krantz, S.B., and L. Jacobson. 1970. Erythropoietin and the Regulation of Erythropoiesis. Univ. of Chicago P., Chicago.Google Scholar
  2. 2.
    Burlington, H., E.P. Cronkite, U. Reinecke, and E.D. Zanjani. 1972. Erythropoietin production in cultures of goat renal glomeruli. Proc Natl. Acad. Sci. USA. 69: 3547–3550.PubMedCrossRefGoogle Scholar
  3. 3.
    Kurtz, A., W. Jelkmann, F. Sinowatz, and C. Bauer. 1983. Renal-mesangial cell cultures as a model for study of erythropoietin production. Proc. Natl. Acad. Sci. USA. 80: 4008–4011.PubMedCrossRefGoogle Scholar
  4. 4.
    Sherwood, J.B., S.H. Robinson, L.R. Bassan, S. Rosen, and A.S. Gordon. 1972. Production of erythrogenin by organ cultures of rat kidney. Blood 40: 189–197.PubMedGoogle Scholar
  5. 5.
    Sherwood, J.B., and E. Goldwasser. 1976. Erythropoietin production by human renal carcinoma cells in culture. Endocrinology 99: 504–510.PubMedCrossRefGoogle Scholar
  6. 6.
    Sherwood, J.B., and D. Shouval. 1986. Continuous production of erythropoietin by an established human renal cell line: Development of the cell line. Proc. Natl. Acad. Sci. USA. 83: 165–169.PubMedCrossRefGoogle Scholar
  7. 7.
    Hagiwara, M., I-Li Chen, R. McGonigle, B. Beckman, F.H. Kasten, and J. M. Fisher. 1984. Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice. Blood 63: 828–835.PubMedGoogle Scholar
  8. 8.
    Sytkowski, A.J., J. P. Richie, and K.A. Bicknell. 1983. New human renal carcinoma cell line established from a patient with erythrocytosis. Cancer Res. 43: 1415–1419.PubMedGoogle Scholar
  9. 9.
    Ascensao, J.L., F. Gaylis, D. Bronson, E.E. Fraley, and E.D. Zanjani. 1983. Erythropoietin production by a human testicular germ cell line. Blood. 62: 1132–1143.PubMedGoogle Scholar
  10. 10.
    Choppin, J., C. Lacombe, N. Casadevall, D. Muller, P. Tambourin, and B. Varet. 1984. Characterization of erythropoietin produced by IW32 murine erythroleukemia cells. Blood 64: 341–347.PubMedGoogle Scholar
  11. 11.
    Shouval, D., B. Rager-Zisman, P. Quan, D.A. Shafritz, B.R. Bloom, and L.M. Reid. 1983. Role in nude mice of interferon and NK cells in inhibiting tumorigenicity of human epatocellular carcinoma cells infected with hepatitis B virus. J. Clin. Invest. 72: 707–717.PubMedCrossRefGoogle Scholar
  12. 12.
    Southern, E.M. 1975. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98: 503–517.PubMedCrossRefGoogle Scholar
  13. 13.
    Firminger, H.I. 1975. Atlas of Tumor Pathology. In: Armed Forces Institute of Pathology, Wash. D.C.Google Scholar
  14. 14.
    Iscove, N.N., F. Sieber, and K.H. Winterhalter. 1974. Erythroid colony formation in cultures of mouse and human bone marrow: analysis of the requirement for erythropoietin by gel filtration and affinity chromatography on agarose-concanavalin A. J. Cell Physiol. 83: 309–320.PubMedCrossRefGoogle Scholar
  15. 15.
    Shouval, D., M. Anton, E. Galun, and J.B. Sherwood. 1988. Erythropoietin induced polycythemia in athymic mice following transplantation of human renal carcinoma cell line. Cancer Research 48: In Press.Google Scholar
  16. 16.
    Sherwood, J.B., and E. Goldwasser. 1978. Extraction of erythropoietin from normal kidneys. Endocrinology 103: 866–870.PubMedCrossRefGoogle Scholar
  17. 17.
    Sherwood, L.M. 1984. Ectopic hormone syndromes. In: Contemporary Endocrinology, Vol. II. S.H. Ingbar, ed., Plenum Press, New York. 345–402.Google Scholar
  18. 18.
    Sutherland, E.W. 1970. On the biological role of cAMP. JAMA 214: 1281–1288.PubMedCrossRefGoogle Scholar
  19. 19.
    Brown, E.M., and G.D. Aurbach. 1980. Role of cyclic nucleotides in secretory mechanisms and actions of parathyroid hormone and calcitonin. Vitamins Hormones 38: 206.Google Scholar
  20. 20.
    Abe, M., and L.M. Sherwood. 1972. Regulation of parathyroid hormone secretion by adenyl cyclase. Biochem. Biophys. Res. Commun. 48: 396–401.PubMedCrossRefGoogle Scholar
  21. 21.
    Brown, E.M., S. Hurwitz, and G.D. Aurbach. 1977. Beta-adrenergic stimulation of cyclic AMP content and parathyroid hormone release from isolated bovine parathyroid cells. Endocrinology 100: 1696.PubMedCrossRefGoogle Scholar
  22. 22.
    Williams, G.A., G.K. Hargis, E.N. Bowser, W.J. Henderson, and N.J. Martinez. 1973. Evidence for a role of adenosine 3’5’-mono-phosphate in parathyroid hormone release. Endocrinology 92: 687–691.PubMedCrossRefGoogle Scholar
  23. 23.
    Kraicer, J., and A.E.H. Chow. 1982. Release of growth hormone from purified somatotrophs: Use of perifusion system to elucidate interrelations among calcium, adenosine 31,51-monophosphate, and somatostatin. Endocrinology 111: 1173–1180.PubMedCrossRefGoogle Scholar
  24. 24.
    Schofield, J.G. 1967. Role of cyclic 35’-adenosine monophosphate in the release of growth hormone in vitro. Nature 215: 1382–1383.PubMedCrossRefGoogle Scholar
  25. 25.
    Tonoue, T., and J. Kitoh. 1978. Release of cyclic AMP from the chicken thyroid stimulated with TSH in vitro. Endocrinol. Jpn. 25: 105–109.PubMedCrossRefGoogle Scholar
  26. 26.
    Robison, G.A., R.W. Butcher, and E.W. Sutherland. 1971. Cyclic AMP. In: Academic Press, Orlando, Florida.Google Scholar
  27. 27.
    Posternak, T., and G. Cehovic. 1971. Derivatives and analogues of cyclic nucleotides. Ann. N.Y. Acad. Sci. 185: 42–49.PubMedCrossRefGoogle Scholar
  28. 28.
    Sherwood, J.B., E.R. Burns, and D. Shouval. 1987. Stimulation by cAMP of erythropoietin secretion by an established human renal carcinoma cell line. Blood 69: 1053–1057.PubMedGoogle Scholar
  29. 29.
    Free, C.A., M. Chasin, V.S. Paik, and S.M. Hess. 1971. Steroidogenic and lipolytic activities of 8-substituted derivatives of cyclic 3’,5’-adenosine monophosphate. Biochem. 10: 3785–3789.CrossRefGoogle Scholar
  30. 30.
    Sherwood, J.B. 1985. cAMP-stimulated release of erythropoietin by normal and neoplastic renal cells. Blood 66: 161 (Abstr.)Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Daniel Shouval
    • 1
  • Judith B. Sherwood
    • 2
  1. 1.The Liver Unit, Department of Medicine AHadassah University HospitalJerusalemIsrael
  2. 2.Division of Hematology, Department of MedicineAlbert Einstein College of MedicineBronxUSA

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