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首页> 外文期刊>Molecular Carcinogenesis >Induction of murine leukemia and lymphoma by dominant negative retinoic acid receptor alpha.
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Induction of murine leukemia and lymphoma by dominant negative retinoic acid receptor alpha.

机译：显性负视黄酸受体α诱导鼠白血病和淋巴瘤。

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Acute promyelocytic leukemia (APL) is invariably associated with chromosomal translocation to retinoic acid receptor alpha (RARalpha) locus. In a vast majority of cases, RARalpha translocates to and fuses with the promyelocytic leukemia (PML) gene. It was thought that the fusion protein PML-RARalpha acts as a double dominant negative mutant to inhibit the PML and RARalpha signaling. In an attempt to study the physiological role of retinoic acid in mammary gland development, we created a transgenic model system expressing a dominant negative RARalpha under the regulation of murine mammary tumor viral promoter. We found that the transgene was also targeted to the lymphoid system in addition to mammary gland. Here we showed that dominant negative RARalpha induced acute lymphoblastic leukemia and lymphoma development in the transgenic mice. Retinoic acid blocked tumor development ex vivo through induction of apoptosis. Thus, our results suggested that disruption of RARalpha signaling was the first essential step in the development of APL in vivo.
机译：急性早幼粒细胞白血病（APL）始终与染色体易位到视黄酸受体α（RARalpha）位点相关。在大多数情况下，RARalpha易位并与早幼粒细胞白血病（PML）基因融合。认为融合蛋白PML-RARalpha充当双重显性负突变体，以抑制PML和RARalpha信号传导。为了研究视黄酸在乳腺发育中的生理作用，我们创建了一个在鼠乳腺肿瘤病毒启动子调控下表达显性负性RARalpha的转基因模型系统。我们发现，除乳腺外，转基因还靶向淋巴系统。在这里，我们显示了显性阴性RARalpha在转基因小鼠中诱导了急性淋巴细胞白血病和淋巴瘤的发展。维甲酸通过诱导细胞凋亡来阻断肿瘤的体外发展。因此，我们的结果表明，RARalpha信号的破坏是体内APL发展的第一步。

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