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Myeloid differentiation and retinoblastoma phosphorylation changes in HL-60
cells induced by retinoic acid receptor- and retinoid X receptor- selective
retinoic acid analogs
SC Brooks , S Kazmer, AA Levin and A Yen
Department of Pathology, Cornell University, Ithaca, NY 14853, USA.
The ability of subtypes of retinoic acid receptors (RARs) and retinoid X
receptors (RXRs) singly and in combination to elicit myeloid
differentiation, G1/0-specific growth arrest, and retinoblastoma (RB) tumor
suppressor protein dephosphorylation was determined in the human
myeloblastic leukemia cell line HL-60 using subtype-selective retinoic acid
(RA) analogs. RA analogs that selectively bind only to RARs (Am580 and/or
TTNPB) or to RXRs (Ro 25-6603, SR11237, and/or SR11234) did not elicit the
above-mentioned three cellular responses. In contrast, simultaneous
treatment with both an RAR-selective ligand (Am580 or TTNPB) and an
RXR-selective ligand (Ro 25-6603, SR11237, or SR11234) induced all three
cellular processes. An RAR alpha-selective ligand used with an
RXR-selective ligand generated the same responses as did all-trans RA or
9-cis RA, which affect both families of receptors, suggesting an important
role for RAR alpha among RAR subtypes in eliciting cellular response.
Consistent with this finding, the RAR alpha antagonist, Ro 41-5253, reduced
the level of the cellular responses elicited by treatment with an RAR
alpha-selective ligand plus RXR-selective ligand. The coupling of the shift
of RB to its hypophosphorylated form with G1/0 arrest and differentiation
in response to ligands is consistent with a possible role of RB as a
downstream target or effector of RAR alpha and RXR in combination.
Volume 87,
Issue 1,
pp. 227-237,
01/01/1996
Copyright © 1996 by The American Society of Hematology

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