Home LiteratureArticle Details
PMID: 6313760 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of transferrin receptor expression on human leukemic cells during proliferation and induction of differentiation. Effects of gallium and dimethylsulfoxide.

The Journal of clinical investigation ·Vol. 72 ·No. 4 ·1983-10-00 ·Pages 1314-25

Chitambar CR, Massey EJ, Seligman PA

Abstract

The association of transferrin receptor expression with cellular proliferation has been studied extensively, but a number of events have not been defined. We therefore assayed receptor on promyelocytic leukemia (HL-60) cells at early times after exposure to a stimulus for proliferation (subculture), as well as agents that either induce differentiation (dimethylsulfoxide [DMSO] ) or inhibit iron uptake (transferrin-gallium). Within 4 h after subculture, we found that a significant increase in total cellular immunoreactive receptor occurred that preceded by 8 h the increase in cell-surface transferrin binding. Automated fluorocytometric analysis of cells in an immunofluorescent assay indicated that increased surface receptor density appeared on cells in the S, G2, and M phases of the cell cycle. DMSO-treated cells proliferated at the same rate as untreated (control) cells for the first 72 h, but as early as 12 h after treatment transferrin receptor was significantly decreased (65% of control cells). Further decreases occurred at later time points until transferrin receptor was undetectable after 7 d, when proliferation had ceased, cells were arrested in G1 phase of the cell cycle, and myeloid differentiation occurred. After exposure to transferrin-gallium, proliferation ceased, but cells exhibited increased surface receptor and were arrested at S phase of the cell cycle without associated myeloid differentiation. We conclude that events preceding cell division provide the regulatory stimulus for the synthesis and subsequent appearance of the transferrin receptor on the cell surface. Additionally, decreased receptor expression may be important in causing cessation of proliferation and/or differentiation. Finally, the way in which gallium salts are currently being investigated as chemotherapeutic agents should be reevaluated in light of our findings concerning transferrin-gallium effects on cellular proliferation.

MeSH Terms
Antibodies, Monoclonal/physiology Cell Line Cell Transformation, Neoplastic/drug effects,metabolism,pathology Dimethyl Sulfoxide/pharmacology Flow Cytometry Gallium/pharmacology Humans Leukemia, Myeloid, Acute/metabolism,pathology Mitosis/drug effects Receptors, Cell Surface/analysis,drug effects,immunology Receptors, Transferrin
Chemicals
Antibodies, Monoclonal Receptors, Cell Surface Receptors, Transferrin Gallium gallium nitrate Dimethyl Sulfoxide
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chitambar C R
Massey E J
Seligman P A
References (42)
42 references, click to expand
  1. Antitumor activity and toxicity of salts of inorganic group 3a metals: aluminum, gallium, indium, and thallium.
    Proc Natl Acad Sci U S A. 1971 Jul;68(7):1623-6 PMID: 5283954
  2. Biological effects of transferrin on human lymphocytes in vitro.
    Exp Cell Res. 1972 Sep;74(1):220-6 PMID: 5073311
  3. Fluorescence and light-scattering measurements on hog cholera-infected PK-15 cells.
    Exp Cell Res. 1973 Mar 30;78(1):209-13 PMID: 4570582
  4. The reaction of ferric salts with transferrin.
    J Biol Chem. 1973 May 10;248(9):3228-32 PMID: 4735577
  5. Rapid, simultaneous measurement of DNA, protein, and cell volume in single cells from large mammalian cell populations.
    J Cell Biol. 1973 Dec;59(3):766-71 PMID: 4128323
  6. Nitroblue-tetrazolium tests.
    Lancet. 1974 Nov 23;2(7891):1248-52 PMID: 4139481
  7. Gallium-67 citrate uptake by cultured tumor cells, stimulated by serum transferrin.
    J Natl Cancer Inst. 1975 May;54(5):1263-6 PMID: 1168730
  8. Analysis of cell populations with a fluorescence-activated cell sorter.
    Ann N Y Acad Sci. 1975 Jun 30;254:163-71 PMID: 52308
  9. Replacement of serum by hormones permits growth of cells in a defined medium.
    Nature. 1976 Jan 15;259(5539):132-4 PMID: 813153
  10. Structure and function of transferrin.
    Prog Hematol. 1975;9:25-56 PMID: 766075
  11. Insulin receptors in normal and transformed fibroblasts: relationship to growth and transformation.
    Cell. 1976 Jul;8(3):417-23 PMID: 954096
  12. Iron salts and transferrin are specifically required for cell division of cultured 3T6 cells.
    Biochem Biophys Res Commun. 1977 Apr 11;75(3):556-62 PMID: 301024
  13. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture.
    Nature. 1977 Nov 24;270(5635):347-9 PMID: 271272
  14. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds.
    Proc Natl Acad Sci U S A. 1978 May;75(5):2458-62 PMID: 276884
  15. Transferrin receptors during rabbit reticulocyte maturation.
    Biochim Biophys Acta. 1979 Apr 18;584(1):76-83 PMID: 221049
  16. Isolation and characterization of the transferrin receptor from human placenta.
    J Biol Chem. 1979 Oct 25;254(20):9943-6 PMID: 226547
  17. Transferrin receptor in human placental brush border membranes. Studies on the binding of transferrin to placental membrane vesicles and the identification of a placental brush border glycoprotein with high affinity for transferrin.
    J Biol Chem. 1979 Dec 25;254(24):12629-35 PMID: 227903
  18. Identification of transferrin receptors on the surface of human cultured cells.
    Proc Natl Acad Sci U S A. 1979 Dec;76(12):6406-10 PMID: 230508
  19. Replacement of serum by insulin and transferrin supports growth and differentiation of the human promyelocytic cell line, HL-60.
    Exp Cell Res. 1980 Apr;126(2):494-8 PMID: 6988226
  20. Transferrin receptors on the human placental microvillous membrane.
    J Clin Invest. 1980 May;65(5):1182-91 PMID: 6245107
  21. Modulation of cell surface iron transferrin receptors by cellular density and state of activation.
    J Supramol Struct. 1979;11(4):579-86 PMID: 232525
  22. Human cell-surface glycoprotein with unusual properties.
    Nature. 1980 Aug 28;286(5776):888-91 PMID: 7412870
  23. Receptor-mediated endocytosis of transferrin in developmentally totipotent mouse teratocarcinoma stem cells.
    J Biol Chem. 1981 Apr 10;256(7):3245-52 PMID: 6259157
  24. Human cell surface glycoprotein related to cell proliferation is the receptor for transferrin.
    Proc Natl Acad Sci U S A. 1981 May;78(5):3039-43 PMID: 6265934
  25. Radioimmunochemical measurement of the transferrin receptor in human trophoblast and reticulocyte membranes with a specific anti-receptor antibody.
    Proc Natl Acad Sci U S A. 1981 Jul;78(7):4222-5 PMID: 6270664
  26. Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin.
    Proc Natl Acad Sci U S A. 1981 Jul;78(7):4515-9 PMID: 6270680
  27. Biosynthesis of the human transferrin receptor in cultured cells.
    J Biol Chem. 1981 Dec 25;256(24):12888-92 PMID: 6273413
  28. Expression of transferrin receptors on mitogen-stimulated human peripheral blood lymphocytes: relation to cellular activation and related metabolic events.
    Immunology. 1981 Dec;44(4):703-10 PMID: 6172372
  29. Induction of differentiation of HL-60 cells by dimethyl sulfoxide: evidence for a stochastic model not linked to the cell division cycle.
    Cancer Res. 1982 Feb;42(2):445-9 PMID: 6948604
  30. Clinical applications of gallium in oncology.
    Int J Nucl Med Biol. 1981;8(4):249-55 PMID: 6948781
  31. Relationship of iron metabolism to tumor cell toxicity of stable gallium salts.
    Int J Nucl Med Biol. 1981;8(4):303-13 PMID: 6948785
  32. Coupling of growth arrest and differentiation at a distinct state in the G1 phase of the cell cycle: GD.
    Proc Natl Acad Sci U S A. 1982 Feb;79(3):845-9 PMID: 6174983
  33. Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro.
    Proc Natl Acad Sci U S A. 1982 Feb;79(4):1175-9 PMID: 6280171
  34. Loss of transferrin receptors following induced differentiation of HL-60 promyelocytic leukemia cells.
    Exp Cell Res. 1982 Apr;138(2):429-33 PMID: 6281048
  35. Studies of the transferrin receptor on both human reticulocytes and nucleated human cells in culture: comparison of factors regulating receptor density.
    J Clin Invest. 1982 Apr;69(4):853-65 PMID: 6804495
  36. Regulation of HeLa cell transferrin receptors.
    J Biol Chem. 1982 Sep 10;257(17):10317-23 PMID: 6286649
  37. Terminal differentiation of the human promyelocytic leukemia cell line, HL-60, in the absence of cell proliferation.
    Cancer Res. 1982 Nov;42(11):4421-6 PMID: 6957259
  38. Regulation of transferrin receptor expression in concanavalin A stimulated and Gross virus transformed rat lymphoblasts.
    J Cell Physiol. 1982 Oct;113(1):40-6 PMID: 6290512
  39. Receptor-mediated endocytosis of transferrin and the uptake of fe in K562 cells: identification of a nonlysosomal acidic compartment.
    Proc Natl Acad Sci U S A. 1982 Oct;79(20):6186-90 PMID: 6292894
  40. Automated analysis of reticulocytes using fluorescent staining with both acridine orange and an immunofluorescence technique.
    Am J Hematol. 1983 Feb;14(1):57-66 PMID: 6301264
  41. Treatment of patients with advanced malignant lymphoma using gallium nitrate administered as a seven-day continuous infusion.
    Cancer. 1983 Jun 1;51(11):1982-7 PMID: 6839291
  42. The plasma-to-cell cycle of transferrin.
    J Clin Invest. 1963 Mar;42:314-26 PMID: 13957331
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI111087
Published
1983-10-00
Pages
1314-25
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC370415
Subset
IM
Grants
NIADDK NIH HHS · AM 27039 · United States
External Links
PubMed source DOI: 10.1172/JCI111087 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2