Correlation among nuclear localization of NuMA-RARα, deregulation of gene expression and leukemic phenotype of hCG-NuMA-RARα transgenic mice.
Acute promyelocytic leukemia (APL) is a model system of aberrant transcription in cancer. We sought to elucidate the mechanism of action of the variant fusion NuMA-RARα in APL, using the hCG-NuMA-RARα transgenic model. We report that subcellular localization of NuMA-RARα in transgenic mice is dependent upon its protein expression and transgene dosage. Subcellular localization of the fusion is inversely correlated with extent of gene deregulation at the mRNA level for Cebpα, Cebpɛ and Pu.1. Finally, we report that phenotype onset is correlated with NuMA-RARα copy number; mice with higher copy number developing disease later than those with lower copy number.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Mahadeo A
MA
Sukhai
Mariam
M
Thomas
Soheila A
SA
Hamadanizadeh
Yali
Y
Xuan
Richard A
RA
Wells
Suzanne
S
Kamel-Reid
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000235:genetics; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018628:Gene Dosage; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D021381:Protein Transport; D019076:Transgenes / Q000235:genetics; D020298:U937 Cells
D006063:Chorionic Gonadotropin; C412764:NuMa-RARalpha protein, human; D015514:Oncogene Proteins, Fusion