A redundant oncogenic potential of the retinoic receptor (RAR) alpha, beta and gamma isoforms in acute promyelocytic leukemia.
Alterations of the retinoic acid receptor (RAR)alpha locus are found in 100% of acute promyelocytic leukemia patients, where chromosomal translocations generate the promyelocytic leukemia (PML)-RARalpha chimeric protein. Here, we have investigated the biological properties of the other RAR isoforms (RARbeta and RARgamma), through the generation and characterization of artificial PML-RAR'x' fusion proteins. Surprisingly, we found that all of the RAR isoforms share an identical oncogenic potential in vitro, thus implying that the selection of the RARalpha locus in leukemia patients must occur--rather than through functional differences among the various RAR isoforms-as the consequence of the nuclear architecture of the different RAR loci.
Marinelli
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A
Department of Biomolecular Sciences and Biotechnology, University of Milan, Milan, Italy.
Bossi
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Pelicci
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PG
Minucci
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D000818:Animals; D002460:Cell Line; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D014162:Transfection; D014178:Translocation, Genetic; D000097768:Retinoic Acid Receptor gamma
D020033:Protein Isoforms; D012334:RNA, Neoplasm; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C000607072:Rara protein, mouse; C082925:retinoic acid receptor beta