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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1977 Aug;74(8):3451–3455. doi: 10.1073/pnas.74.8.3451

Tumor promoters inhibit spontaneous and induced differentiation of murine erythroleukemia cells in culture.

H Yamasaki, E Fibach, U Nudel, I B Weinstein, R A Rifkind, P A Marks
PMCID: PMC431603  PMID: 269404

Abstract

Addition of the potent tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), to murine erythroleukemia cell lines in suspension cultures inhibited both spontaneous differentiation and differentiation induced by hexamethylene bisacetamide (HMBA), dimethyl sulfoxide, or butyric acid. Inhibition was unrelated to cytotoxicity and was reversible. When several plant diterpenes were tested, there was a positive correlation between tumor-promoting activity and inhibition of differentiation. TPA inhibited HMBA-induced differentiation only if added prior to the time of commitment to differentiation, as assayed by scoring for differentiation after transfer of cells from HMBA to fresh medium without HMBA. TPA-mediated inhibition of differentiation was associated with a decrease in globin mRNA accumulation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berenblum I. A re-evaluation of the concept of cocarciongenesis. Prog Exp Tumor Res. 1969;11:21–30. doi: 10.1159/000391387. [DOI] [PubMed] [Google Scholar]
  3. Boutwell R. K. The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol. 1974 Jan;2(4):419–443. doi: 10.3109/10408447309025704. [DOI] [PubMed] [Google Scholar]
  4. Boyer S. H., Wuu K. D., Noyes A. N., Young R., Scher W., Friend C., Preisler H. D., Bank A. Hemoglobin biosynthesis in murine virus-induced leukemic cells in vitro: structure and amounts of globin chains produced. Blood. 1972 Dec;40(6):823–835. [PubMed] [Google Scholar]
  5. Cohen R., Pacifici M., Rubinstein N., Biehl J., Holtzer H. Effect of a tumour promoter on myogenesis. Nature. 1977 Apr 7;266(5602):538–540. doi: 10.1038/266538a0. [DOI] [PubMed] [Google Scholar]
  6. Dow L. W., Terada M., Natta C., Metafora S., Grossbard E., Marks P. A., Bank A. Globin synthesis of intact cells and activity of isolated mRNA in -thalassaemia. Nat New Biol. 1973 May 23;243(125):114–116. [PubMed] [Google Scholar]
  7. Ebert P. S., Ikawa Y. Induction of delta-aminolevulinic acid synthetase during erythroid differentiation of cultured leukemia cells. Proc Soc Exp Biol Med. 1974 Jun;146(2):601–604. doi: 10.3181/00379727-146-38155. [DOI] [PubMed] [Google Scholar]
  8. Eisen H., Nasi S., Georgopoulos C. P., Arndt-Jovin D., Ostertag W. Surface changes in differentiating Friend erythroleukemic cells in culture. Cell. 1977 Apr;10(4):689–695. doi: 10.1016/0092-8674(77)90102-7. [DOI] [PubMed] [Google Scholar]
  9. Fibach E., Reuben R. C., Rifkind R. A., Marks P. A. Effect of hexamethylene bisacetamide on the commitment to differentiation of murine erythroleukemia cells. Cancer Res. 1977 Feb;37(2):440–444. [PubMed] [Google Scholar]
  10. Friend C., Scher W., Holland J. G., Sato T. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378–382. doi: 10.1073/pnas.68.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gusella J., Geller R., Clarke B., Weeks V., Housman D. Commitment to erythroid differentiation by friend erythroleukemia cells: a stochastic analysis. Cell. 1976 Oct;9(2):221–229. doi: 10.1016/0092-8674(76)90113-6. [DOI] [PubMed] [Google Scholar]
  12. Harrison P. R., Gilmour R. S., Affara N. A., Conkie D., Paul J. Globin messenger RNA synthesis and processing during haemoglobin induction in Friend cells. II. Evidence for post-transcriptional control in clone 707. Cell Differ. 1974 Jun;3(1):23–30. doi: 10.1016/0045-6039(74)90037-2. [DOI] [PubMed] [Google Scholar]
  13. Kacian D. L., Gambino R., Dow L. W., Grossbard E., Natta C., Ramirez F., Spiegelman S., Marks P. A., Bank A. Decreased globin messenger RNA in thalassemia detected by molecular hybridization. Proc Natl Acad Sci U S A. 1973 Jun;70(6):1886–1890. doi: 10.1073/pnas.70.6.1886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kimhi Y., Palfrey C., Spector I., Barak Y., Littauer U. Z. Maturation of neuroblastoma cells in the presence of dimethylsulfoxide. Proc Natl Acad Sci U S A. 1976 Feb;73(2):462–466. doi: 10.1073/pnas.73.2.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Leder A., Leder P. Butyric acid, a potent inducer of erythroid differentiation in cultured erythroleukemic cells. Cell. 1975 Jul;5(3):319–322. doi: 10.1016/0092-8674(75)90107-5. [DOI] [PubMed] [Google Scholar]
  16. Leder A., Leder P. Butyric acid, a potent inducer of erythroid differentiation in cultured erythroleukemic cells. Cell. 1975 Jul;5(3):319–322. doi: 10.1016/0092-8674(75)90107-5. [DOI] [PubMed] [Google Scholar]
  17. Levy J., Terada M., Rifkind R. A., Marks P. A. Induction of erythroid differentiation by dimethylsulfoxide in cells infected with Friend virus: relationship to the cell cycle. Proc Natl Acad Sci U S A. 1975 Jan;72(1):28–32. doi: 10.1073/pnas.72.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nudel U., Salmon J. E., Terada M., Bank A., Rifkind R. A., Marks P. A. Differential effects of chemical inducers on expression of beta globin genes in murine erythroleukemia cells. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1100–1104. doi: 10.1073/pnas.74.3.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ohta Y., Tanaka M., Terada M., Miller O. J., Bank A., Marks P., Rifkind R. A. Erythroid cell differentiation: murine erythroleukemia cell variant with unique pattern of induction by polar compounds. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1232–1236. doi: 10.1073/pnas.73.4.1232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ostertag W., Melderis H., Steinheider G., Kluge N., Dube S. Synthesis of mouse haemoglobin and globin mRNA in leukaemic cell cultures. Nat New Biol. 1972 Oct 25;239(95):231–234. doi: 10.1038/newbio239231a0. [DOI] [PubMed] [Google Scholar]
  21. Palfrey C., Kimhi Y., Littauer U. Z. Induction of differentiation in mouse neuroblastoma cells by hexamethylene bisacetamide. Biochem Biophys Res Commun. 1977 Jun 6;76(3):937–942. doi: 10.1016/0006-291x(77)91592-3. [DOI] [PubMed] [Google Scholar]
  22. Reuben R. C., Wife R. L., Breslow R., Rifkind R. A., Marks P. A. A new group of potent inducers of differentiation in murine erythroleukemia cells. Proc Natl Acad Sci U S A. 1976 Mar;73(3):862–866. doi: 10.1073/pnas.73.3.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ross J., Ikawa Y., Leder P. Globin messenger-RNA induction during erythroid differentiation of cultured leukemia cells. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3620–3623. doi: 10.1073/pnas.69.12.3620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ross J., Ikawa Y., Leder P. Globin messenger-RNA induction during erythroid differentiation of cultured leukemia cells. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3620–3623. doi: 10.1073/pnas.69.12.3620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rovera G., Bonaiuto J. The phenotypes of variant clones of Friend mouse erythroleukemic cells resistant to dimethyl sulfoxide. Cancer Res. 1976 Nov;36(11 Pt 1):4057–4061. [PubMed] [Google Scholar]
  26. Rovera G., O'Brien T. G., Diamond L. Tumor promoters inhibit spontaneous differentiation of Friend erythroleukemia cells in culture. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2894–2898. doi: 10.1073/pnas.74.7.2894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Singer D., Cooper M., Maniatis G. M., Marks P. A., Rifkind R. A. Erythropoietic differentiation in colonies of cells transformed by Friend virus. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2668–2670. doi: 10.1073/pnas.71.7.2668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Terada M., Fried J., Nudel U., Rifkind R. A., Marks P. A. Transient inhibition of initiation of S-phase associated with dimethyl sulfoxide induction of murine erythroleukemia cells to erythroid differentiation. Proc Natl Acad Sci U S A. 1977 Jan;74(1):248–252. doi: 10.1073/pnas.74.1.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Van Duuren B. L. Tumor-promoting agents in two-stage carcinogenesis. Prog Exp Tumor Res. 1969;11:31–68. doi: 10.1159/000391388. [DOI] [PubMed] [Google Scholar]
  30. Wigler M., Weinstein I. B. Tumour promotor induces plasminogen activator. Nature. 1976 Jan 22;259(5540):232–233. doi: 10.1038/259232a0. [DOI] [PubMed] [Google Scholar]

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