Orchiectomy reduces hepatotumorigenesis of H-ras12V transgenic mice via the MAPK pathway.

Orchiectomy reduces hepatotumorigenesis of H-ras12V transgenic mice via the MAPK pathway.
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睾丸切除术通过 MAPK 途径减少 H-ras12V 转基因小鼠的肝肿瘤发生。

DOI:
10.1016/j.lfs.2006.06.032
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发表时间:
2006
期刊:
影响因子:
6.1
通讯作者:
Dong
Dong
中科院分区:
医学2区
文献类型:
--
作者:
Ai;H. Moon;S. Chun;Tae;Dae;Dong

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人类和动物肝细胞癌的一个共同特征是男性患病率高。然而,潜在的机制在很大程度上仍然未知。我们报道过,在雄性H-ras12V转基因小鼠中,肝肿瘤的发生是普遍的()。进行睾丸切除术和卵巢切除术以确定性器官相关因素的存在是否有助于肝肿瘤的发生。在切除睾丸和卵巢后,小鼠在6个月大时取样。检测病理诊断、性激素水平、H-ras12V转基因基因表达及ras相关信号通路。睾丸切除术显著降低了男性肝肿瘤发生的发生率。然而,在卵巢切除和未卵巢切除的女性中,肿瘤发生的发生率没有显著差异。分子生化实验表明,性器官相关因子显著影响转基因表达,促进MAPK信号通路的激活。本研究表明,睾丸相关因素在H-ras12V转基因小鼠的肝肿瘤发生中起重要作用。
A common characteristic of hepatocellular carcinoma in humans and animals is a striking male prevalence. However, the underlying mechanisms remain largely unknown. We have reported that hepatotumorigenesis is prevalent in male H-ras12V transgenic mice (). Orchiectomy and ovariectomy were performed to determine if the presence of sex organ-related factors contributes to hepatotumorigenesis. After orchiectomy and ovariectomy, the mice were sampled at 6 months of age. The pathological diagnosis, sex hormone levels, expression of the H-ras12V transgene, and ras related signal pathways were determined. Orchiectomy significantly reduced the incidence of hepatotumorigenesis in males. However, no significant difference was detected in the incidence of tumorigenesis between ovariectomized and non-ovariectomized females. Molecular biochemical experiments showed that the sex organ-related factors significantly influenced transgene expression, which contributed to activation of the MAPK signaling pathway. The present study demonstrates that testis-related factors play important roles in hepatotumorigenesis in H-ras12V transgenic mice.
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