Retinoic acid receptors in myeloid leukemia: characterization of receptors
in retinoic acid-resistant K-562 cells
KA Robertson, L Mueller and SJ Collins
Molecular Medicine Program, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
Although mRNA for the retinoic acid receptor alpha (RAR-alpha) is expressed
in many different myeloid leukemias, most of these leukemia cells exhibit
little if any phenotypic response when exposed to retinoic acid (RA). To
determine whether such RA resistance is related to altered RA receptor
structure or function, we performed a detailed analysis of nuclear RA
receptors in RA-resistant K-562 cells. These cells exhibit RA receptors of
the same approximate molecular weight and similar kd as those exhibited by
the RA-sensitive HL-60 leukemia cell line, but the number of RA receptors
in the RA-resistant K-562 cells (80 per cell) is significantly lower than
that exhibited by RA- sensitive HL-60 cells (550 per cell).
Retroviral-mediated transduction of RAR-alpha cDNA into K-562 significantly
increased the number of RA receptors to 2,000 per cell. These
RAR-alpha-transduced K-562 cells, when incubated with RA, exhibit
diminished cell proliferation associated with decreased c-myc expression
and an accumulation of cells in G0/G1. In addition, these RA-treated cells
exhibit downregulation of the CD15 surface antigen and a slight increase in
hemoglobin production but manifest no other evidence of significant
erythroid, megakaryocytic, or myeloid differentiation. These results
indicate that an elevated number of nuclear RA receptors can be involved in
altering proliferation but not necessarily the differentiation of certain
RA- treated myeloid leukemia cells.
Volume 77,
Issue 2,
pp. 340-347,
01/15/1991
Copyright © 1991 by The American Society of Hematology
