Differential regulation of JunD by dihydroxycholecalciferol in human chronic myelogenous leukemia cells.
1,25-Dihydroxyvitamin D3 inhibits the proliferation of the chronic myelogenous leukemia cell line RWLeu-4 but not the resistant variant, JMRD3. 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 D3-response element are noted. It is shown herein that the 1,25-dihydroxyvitamin D3 receptor binds to the osteocalcin-1,25-dihydroxyvitamin D3-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 D3. It is shown that JunD DNA binding activity is enhanced by 1,25-dihydroxyvitamin D3 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.
Lasky
S R
SR
Roger Williams Medical Center, Section of Experimental Pathology, Providence, Rhode Island 02908, USA.
Iwata
K
K
Rosmarin
A G
AG
Caprio
D G
DG
Maizel
A L
AL
D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018167:Receptors, Calcitriol; D018808:Transcription Factor AP-1; D002117:Calcitriol