Huntingtin Overexpression Does Not Alter Overall Survival in Murine Cancer Models.

IF 2.1 Q3 NEUROSCIENCES Journal of Huntington's disease Pub Date : 2022-01-01 DOI:10.3233/JHD-220554
Laura Lynn Chan, Austin Hill, Ge Lu, Jeremy Van Raamsdonk, Randy Gascoyne, Michael R Hayden, Blair R Leavitt
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Abstract

A reduced incidence of various forms of cancer has been reported in Huntington's disease patients and may be due to pro-apoptotic effects of mutant huntingtin. We tested this hypothesis by assessing the effects of huntingtin protein overexpression on survival in two murine cancer models. We generated YAC HD mice containing human huntingtin transgenes with various CAG tract lengths (YAC18, YAC72, YAC128) on either an Msh2 or p53 null background which have increased cancer incidence. In both mouse models of cancer, the overexpression of either mutant or wild-type huntingtin had no significant effect on overall survival. These results do not support the hypothesis that mutant huntingtin expression is protective against cancer.

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亨廷顿蛋白过表达不会改变小鼠癌症模型的总生存率。
据报道,在亨廷顿氏病患者中,各种形式的癌症发病率降低,这可能是由于突变的亨廷顿蛋白的促凋亡作用。我们通过评估两种小鼠癌症模型中亨廷顿蛋白过表达对生存的影响来验证这一假设。我们在Msh2或p53基因缺失的背景下,培养了具有不同CAG束长度(YAC18, YAC72, YAC128)的含有人类亨廷顿蛋白转基因的YAC HD小鼠,这些小鼠的癌症发病率增加。在两种小鼠癌症模型中,突变型或野生型亨廷顿蛋白的过表达对总生存率没有显著影响。这些结果不支持突变的亨廷顿蛋白表达可以预防癌症的假设。
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来源期刊
CiteScore
4.80
自引率
9.70%
发文量
60
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