Skip to main content
NCBI home page
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 Jul;74(7):2894–2898. doi: 10.1073/pnas.74.7.2894

Tumor promoters inhibit spontaneous differentiation of Friend erythroleukemia cells in culture.

G Rovera, T G O'Brien, L Diamond
PMCID: PMC431336  PMID: 268640

Abstract

Clones of Friend erythroleukemia cells, characterized by the presence of 40-70% benzidine-positive cells synthesizing hemoglobin in the absence of inducing drugs, were treated with several phorbol diesters with a known range of tumor-promoting activity on mouse skin. Good correlation was found between the reported tumor-promoting activity of a particular phorbol diester and its ability to inhibit spontaneous erythroid differentiation in culture. The inhibition of differentiation by 12-O-tetradecanoyl-phorbol-13-acetate, the most active tumor promoter, was maximum after 4 days of treatment; this inhibition was reversed by removal of the phorbol diester no matter how long the period of treatment. Unlike control cells, which gradually revert to a population with a low percentage of benzidine-positive cells, cells treated with 12-O-tetradecanoyl-phorbol-13-acetate retained a high potential for spontaneous differentiation.

Full text

PDF
2894

Images in this article

2897Image
on p.2897

Selected References

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

  1. Baird W. M., Boutwell R. K. Tumor-promoting activity of phorbol and four diesters of phorbol in mouse skin. Cancer Res. 1971 Aug;31(8):1074–1079. [PubMed] [Google Scholar]
  2. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [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. 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]
  5. Diamond L., O'Brien S., Donaldson C., Shimizu Y. Growth stimulation of human diploid fibro-blasts by the tumor promoter, 12-0-tetradecanoly-phorbol-13-acetate. Int J Cancer. 1974 May 15;13(5):721–730. doi: 10.1002/ijc.2910130516. [DOI] [PubMed] [Google Scholar]
  6. Friend C., Preisler H. D., Scher W. Studies on the control of differentiation of murine virus-induced erythroleukemic cells. Curr Top Dev Biol. 1974;8:81–101. doi: 10.1016/s0070-2153(08)60606-7. [DOI] [PubMed] [Google Scholar]
  7. Harrison P. R. Analysis of erythropoeisis at the molecular level. Nature. 1976 Jul 29;262(5567):353–356. doi: 10.1038/262353a0. [DOI] [PubMed] [Google Scholar]
  8. Kabat D., Sherton C. C., Evans L. H., Bigley R., Koler R. D. Synthesis of erythrocyte-specific proteins in cultured friend leukemia cells. Cell. 1975 Jul;5(3):331–338. doi: 10.1016/0092-8674(75)90109-9. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Laskey R. A., Mills A. D. Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. Eur J Biochem. 1975 Aug 15;56(2):335–341. doi: 10.1111/j.1432-1033.1975.tb02238.x. [DOI] [PubMed] [Google Scholar]
  11. Marks F. Epidermal growth control mechanisms, hyperplasia, and tumor promotion in the skin. Cancer Res. 1976 Jul;36(7 Pt 2):2636–2643. [PubMed] [Google Scholar]
  12. Mondal S., Brankow D. W., Heidelberger C. Two-stage chemical oncogenesis in cultures of C3H/10T1/2 cells. Cancer Res. 1976 Jul;36(7 Pt 1):2254–2260. [PubMed] [Google Scholar]
  13. Mondal S., Heidelberger C. Transformation of C3H/10T1/2CL8 mouse embryo fibroblasts by ultraviolet irradiation and a phorbol ester. Nature. 1976 Apr 22;260(5553):710–711. doi: 10.1038/260710a0. [DOI] [PubMed] [Google Scholar]
  14. Orkin S. H., Harosi F. I., Leder P. Differentiation in erythroleukemic cells and their somatic hybrids. Proc Natl Acad Sci U S A. 1975 Jan;72(1):98–102. doi: 10.1073/pnas.72.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Raick A. N. Cell differentiation and tumor-promoting action in skin carcinogenesis. Cancer Res. 1974 Nov;34(11):2915–2925. [PubMed] [Google Scholar]
  16. 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]
  17. Sivak A., Van Duuren B. L. A cell culture system for the assessment of tumor-promoting activity. J Natl Cancer Inst. 1970 May;44(5):1091–1097. [PubMed] [Google Scholar]
  18. Trosko J. E., Chang C. C., Yotti L. P., Chu E. H. Effect of phorbol myristate acetate on the recovery of spontaneous and ultraviolet light-induced 6-thioguanine and ouabain-resistant Chinese hamster cells. Cancer Res. 1977 Jan;37(1):188–193. [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Yuspa S. H., Lichti U., Ben T., Patterson E., Hennings H., Slaga T. J., Colburn N., Kelsey W. Phorbol esters stimulate DNA synthesis and ornithine decarboxylase activity in mouse epidermal cell cultures. Nature. 1976 Jul 29;262(5567):402–404. doi: 10.1038/262402a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES