DOWN-REGULATION OF NM23.H1, NM23.H2 AND C-MYC GENES DURING DIFFERENTIATION-INDUCED BY 1,25-DIHYDROXYVITAMIN D-3

The NM23 gene, involved in the negative regulation of metastatic progr ession, has been found to be highly homologous to developmentally regu lated genes such as the awd gene in Drosophila melanogaster and the Gi p17 gene in Dyctiostelium discoideum, To ascertain whether the NM23 ge nes are involved in the differentiation processes of human cell lines, the NM23.H1 and NM23.H2 expression level has been determined during t he monocyte-macrophage differentiation of HL-60 and U-937 cell lines i nduced by vitamin D-3. In both lines, vitamin D-3 produced induction o f differentiative markers, inhibition of cell proliferation and a decr ease of the NM23.H1, NM23.H2 and c-myc genes, behaving both as a diffe rentiative and an antiproliferative agent, The fact that the c-myc tra nscriptional factor PuF is identical to the NM23.H2 gene and that NM23 protein could be a transcriptional factor suggests that the regulator y action exerted by vitamin D-3 on c-myc transcription is mediated by NM23.H2.