1,25-Dihydroxyvitamin D inhibits the proliferation of the chronic myelogenous leukemia cell line RWLeu-4 but not the resistant variant, JMRD. Although these cells exhibit no detectable differences in the vitamin D receptor, alterations in the interaction of nuclear extracts with the osteocalcin-1,25-dihydroxyvitamin D-response element are noted. It is shown herein that the 1,25-dihydroxyvitamin D receptor binds to the osteocalcin-1,25-dihydroxyvitamin D-response element along with activator protein-1 (AP-1) complexes and that the DNA binding activities of members of the Jun and Fos proto-oncogene families, which make up the AP-1 transcription factor, are differentially regulated by 1,25-dihydroxyvitamin D. It is shown that JunD DNA binding activity is enhanced by 1,25-dihydroxyvitamin D during cell cycle arrest in the sensitive cells but is decreased in the resistant cells. These results suggest that the level of JunD DNA binding activity may be a critical factor in the regulation of proliferation.

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