Differential regulation of vitamin D receptor expression in distinct leukemic cell lines upon phorbol ester-induced growth arrest

A close correlation between vitamin D receptor (VDR) abundance and cell pro liferation rate has been shown in NIH-3T3 fibroblasts, MCF-7 breast cancer and in HL-60 myeloblastic cells. We have now determined if this association occurs in other leukemic cell lines, U937 and K562, and if VDR content is related to c-myc expression, which is also linked to cell growth state. Upo n phorbol myristate acetate (PMA) treatment, cells from the three lineages (HL-60, U937 and K562) differentiated and expressed specific surface antige ns. All cell lines analyzed were growth inhibited by PMA and the doubling t ime was increased, mainly due to an increased fraction of cells in the G0/G 1 phase, as determined by flow cytometry measurements of incorporated bromo deoxpuridine and cell DNA content. C-myc mRNA expression was down-regulated and closely correlated to cell growth arrest. However, VDR expression in l eukemic cell lines, as determined by immunofluorescence and Northern blot a ssays, was not consistently changed upon inhibition of cell proliferation s ince VDR levels were down-regulated only in HL-60 cells. Our data suggest t hat VDR expression cannot be explained simply as a reflection of the leukem ic cell growth state.