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SR Lasky, MR Posner, K Iwata, A Santos-Moore, A Yen, V Samuel, J Clark and AL Maizel
Department of Pathology and Laboratory Medicine, Roger Williams Medical
Center, Brown University School of Medicine, Providence, RI 02908.
A variant of the chronic myelogenous leukemia cell line, RWLeu-4, that is
resistant to the antiproliferative effects of vitamin D3 was established.
Although RWLeu-4 proliferation is inhibited by 1 nmol/L vitamin D3, the
resistant cells (JMRD3) continue to proliferate in the presence of 100
nmol/L vitamin D3. Both cells express similar patterns of
differentiation-specific antigens after treatment with vitamin D3, and both
express the retinoblastoma gene product (p110Rb). Vitamin D3 treatment of
the sensitive RWLeu-4 cells decreased the level of the p110Rb protein, as
well as its phosphorylation. In contrast, vitamin D3 treatment of JMRD3 had
no effect on p110Rb expression or phosphorylation. Both RWLeu-4 and JMRD3
express similar vitamin D3 receptors and vitamin D3-inducible enzyme
activities. Differences were detected in the DNA binding characteristics of
the vitamin D3 receptors as determined by electrophoretic mobility shift
studies. However, sequence analysis of the DNA-binding domain and
immunoblot analysis showed no differences in the receptors. We conclude
that some process subsequent to vitamin D3 receptor activation is altered
in JMRD3 that partially separates vitamin D3-induced inhibition of
proliferation from the induction of differentiation.
This article has been cited by other articles:
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| Copyright © 1994 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
