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Letters to Nature
Nature 306, 492 - 494 (01 December 1983); doi:10.1038/306492a0

Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite

P. H. Reitsma*, P. G. Rothberg, S. M. Astrin, J. Trial*, Z. Bar-Shavit*, A. Hall*, S. L. Teitelbaum* & A. J. Kahn

*Division of Cell Biology, School of Dental Medicine, and The Departments of Pathology (Jewish Hospital) and Genetics, School of Medicine, Washington University, St Louis, Missouri 63110, USA
Cancer Research Institute, Philadelphia, Pennsylvania 19111, USA
To whom reprint requests should be addressed at the School of Dental Medicine.

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.

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