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

Abstract

A close correlation between vitamin D receptor (VDR) abundance and cell proliferation 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. Upon phorbol myristate acetate (PMA) treatment, cells from the three lineages (HL-60, U937 and K562) differentiated and expressed specific surface antigens. All cell lines analyzed were growth inhibited by PMA and the doubling time was increased, mainly due to an increased fraction of cells in the G0/G1 phase, as determined by flow cytometry measurements of incorporated bromodeoxyuridine and cell DNA content. C-myc mRNA expression was down-regulated and closely correlated to cell growth arrest. However, VDR expression in leukemic cell lines, as determined by immunofluorescence and Northern blot assays, was not consistently changed upon inhibition of cell proliferation since VDR levels were down-regulated only in HL-60 cells. Our data suggest that VDR expression cannot be explained simply as a reflection of the leukemic cell growth state.

Impaired nuclear localization of vitamin D receptor in leukemia cells resistant to calcitriol-induced differentiation

“…We next wanted to determine if resistance of THP-1/DR cells could be caused by loss of vitamin D receptor in the cells. HL-60 cells have been reported to express VDR [16,17] and were therefore used as controls for VDR expression. Western blot analyses revealed that VDR is present in THP-1 cells as well as in THP-1/DR cells (Fig.…”

Effects of vitamin D on the growth of normal and malignant B-cell progenitors

“…VDR expression investigated in frozen B lineage blast cells at diagnosis and before treatment was not detected in all samples tested. As its expression in distinct leukaemic cell lines is regulated differentially upon the effect of proliferation or differentiation inducers [29,30], further investigation should be performed after the beginning of the culture. In addition, as in most antigen expression, the VD receptor is influenced by the cells' relationship with the bone marrow microenvironment [31], and its expression in malignant cryopreserved lymphoblastic cells may not become evident before a brief period of culture.…”

Toxicological screening of Euphorbia tirucalli L.: Developmental toxicity studies in rats

“…The administration of Euphorbia tirucalli latex does not seem to present overt maternal toxicity measurable through clinical signs, but leucopenia was observed in treated group from Experiment II. Folgueira et al (2000) reported that phorbol myristate acetate caused growth inhibition in cell lineage HL-60, U937 and K564. It could be speculated if the leucopenia was a result of mitosis inhibition of the white cells, however, in the present work we were unable to identify the cause of maternal leucopenia.…”