Abstract
HL-60, a cell line established from a patient with promyelocytic leukaemia, responds to a variety of inducing agents by ceasing division and acquiring some of the characteristics of either granulocytes or monocytes1–4. Among the agents so far tested, only a comparative few occur naturally in vertebrates and would appear to have significant clinical potential in the treatment of leukaemic patients. One of the most promising of these is the dihydroxymetabolite of vitamin D3, 1,25(OH)2D3. This compound circulates in normal man and has a major role in calcium homeostasis5. Moreover, it has recently been reported that 1,25(OH)2D3 increases the survival time of mice injected with myeloid leukaemia cells6. We7 and McCarthy et al.8 have previously shown that HL-60 cells respond to near physiological levels of 1,25(OH)2D3 by rapidly acquiring a number of monocyte-like features. Here we document that these phenotypic changes are preceded by a marked decrement in the expression of the c-myc oncogene. In fact, the diminution in the level of c-myc mRNA parallels the dose dependency and metabolite specificity shown by the various other indicators of phenotypic change. In addition, we demonstrate that removal of vitamin D3, after the onset of maturational change, results in the reappearance of elevated myc mRNA levels. We believe this to be the first demonstration of a sequential relationship between the application of an exogenous inducing agent, a reduction in myc mRNA levels and the development of characteristics associated with normal cell maturation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Collins, S. J., Ruscetti, F. W., Gallagher, R. E. & Gallo, R. C. Proc. natn. Acad. Sci. U.S.A. 75, 2458–2462 (1978).
Rovera, G., O'Brien, T. G. & Diamond, L. Science 204, 868–870 (1979).
Breitman, T. R., Selonick, S. E. & Collins, S. J. Proc. natn. Acad. Sci. U.S.A. 77, 2936–2940 (1980).
Elias, L., Wogenrich, F. J., Wallace, J. M. & Longmire, J. Leukemia Res. 4, 301–307 (1980).
Haussler, M. R. & McCain, T. A. New Engl. J. Med. 297, 974–983, 1041–1050 (1977).
Honma, Y. et al. Proc. natn. Acad. Sci. U.S.A. 80, 201–204 (1983).
Bar-Shavit, Z. et al. Proc. natn. Acad. Sci. U.S.A. 80, 5907–5911 (1983).
McCarthy, D. M. et al. Leukemia Res. 7, 51–55 (1983).
Tanaka, H. et al. Biochem. J. 204, 713–719 (1982).
Collins, S. & Groudine, M. Nature 298, 679–681 (1982).
Dalla Favera, R., Wong-Staal, F. & Gallo, R. C. Nature 299, 61–63 (1982).
Westin, E. H. et al. Proc. natn. Acad. Sci. U.S.A. 79, 2490–2494 (1982).
Klein, G. Nature 294, 313–318 (1981).
Ugolini, V., Nunez, G., Smith, R. G., Stastny, P., Capra, J. D. Proc. natn. Acad. Sci. U.S.A. 77, 0664–0668 (1980).
Raff, H. V., Richer, L. J. & Stobo, J. D. J. exp. Med. 152, 581–593 (1980).
Rothberg, P. G., Erisman, M. D., Diehl, R. E., Rovigatti, U. G. & Astrin, S. M. Mol. Cell. Biol. (submitted).
Klein, G. Cell 32, 311–315 (1983).
Maguire, R. T., Robins, T. S., Thorgeirsson, S. S. & Heilman, C. A. Proc. natn. Acad. Sci. U.S.A. 80, 1947–1950 (1983).
Astrin, S. M. & Rovigatti, U. G. International Workshop on the Influence of the Environment on Leukemia and Lymphoma Subtypes (Raven, New York, in the press).
Litwach, G. Proc. Soc. exp. Biol. Med. 89, 401–403 (1955).
Minty, A. T. et al. Biol. Chem. 256, 1008–1014 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Reitsma, P., Rothberg, P., Astrin, S. et al. Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite. Nature 306, 492–494 (1983). https://doi.org/10.1038/306492a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/306492a0
This article is cited by
-
Treatment of K562 cells with 1,25-dihydroxyvitamin D3 induces distinct alterations in the expression of apoptosis-related genes BCL2, BAX, BCLXL, and p21
Annals of Hematology (2010)
-
Characterization of a novel hexameric repeat DNA sequence in the promoter of the immediate early gene, IEX-1, that mediates 1α,25-dihydroxyvitamin D3-associated IEX-1 gene repression
Oncogene (2002)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
