A variant of the chronic myelogenous leukemia cell line, RWLeu-4, that
is resistant to the antiproliferative effects of vitamin D-3 was esta
blished. Although RWLeu-4 proliferation is inhibited by 1 nmol/L vitam
in D-3, the resistant cells (JMRD(3)) continue to proliferate in the p
resence of 100 nmol/L vitamin D-3. Both cells express similar patterns
of differentiation-specific antigens after treatment with vitamin D-3
, and both express the retinoblastoma gene product (p110(Rb)). Vitamin
D-3 treatment of the sensitive RWLeu-4 cells decreased the level of t
he p110(Rb) protein, as well as its phosphorylation. In contrast, vita
min D-3 treatment of JMRD(3) had no effect on p110(Rb) expression or p
hosphorylation. Both RWLeu-4 and JMRD(3) express similar vitamin D-3 r
eceptors and vitamin D-3-inducible enzyme activities. Differences were
detected in the DNA binding characteristics of the vitamin D-3 recept
ors as determined by electrophoretic mobility shift studies, However,
sequence analysis of the DNA-binding domain and immunoblot analysis sh
owed no differences in the receptors. We conclude that some process su
bsequent to vitamin D-3 receptor activation is altered in JMRD(3) that
partially separates vitamin D-3-induced inhibition of proliferation f
rom the induction of differentiation. (C) 1994 by The American Society
of Hematology.