DIFFERENTIAL REGULATION OF JUND BY DIHYDROXYCHOLECALCIFEROL IN HUMAN CHRONIC MYELOGENOUS LEUKEMIA-CELLS

1,25-Dihydroxyvitamin D-3 inhibits the proliferation of the chronic myelogenous leukemia cell Line RWLeu-4 but not the resistant variant, JMRD(3). 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-3-response element are noted, It is shown herein that the 1,25-dihydroxyvitamin D, receptor binds to the osteocalcin-1,25-dihydroxyvitamin D-3-response element along with activator protein-1 (AP-I) 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-3. It is shown that JunD DNA binding activity is enhanced by 1,25-dihydroxyvitamin DQ 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.