Down regulation of NM23.H1, NM23.H2 and c-myc genes during differentiation induced by 1,25 dihydroxyvitamin D3.

The NM23 gene, involved in the negative regulation of metastatic progression, has been found to be highly homologous to developmentally regulated genes such as the awd gene in Drosophila melanogaster and the Gip17 gene in Dyctiostelium discoideum. To ascertain whether the NM23 genes are involved in the differentiation processes of human cell lines, the NM23.H1 and NM23.H2 expression level has been determined during the monocyte-macrophage differentiation of HL-60 and U-937 cell lines induced by vitamin D3. In both lines, vitamin D3 produced induction of differentiative markers, inhibition of cell proliferation and a decrease of the NM23.H1, NM23.H2 and c-myc genes, behaving both as a differentiative and an antiproliferative agent. The fact that the c-myc transcriptional factor PuF is identical to the NM23.H2 gene and that NM23 protein could be a transcriptional factor suggests that the regulatory action exerted by vitamin D3 on c-myc transcription is mediated by NM23.H2.