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首页> 外文期刊>Oncology reports >Kruppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis
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Kruppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis

机译:化学诱导的肝癌发生后,Kruppel样因子10空小鼠表现出较低的肿瘤发生率并抑制了细胞增殖活性

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摘要

Liver cancer is the third most common cancer, and the incidence as well as the mortality rate of liver cancer are on the increase. There are many signaling pathways that are involved in hepatic tumorigenesis. One of these pathways, the transforming growth factor-beta (TGF-beta)/Smad pathway with KLF10, has been reported to suppress cellular proliferation in most cases. However, the actual functions of KLF10 in various pathophysiological conditions are still fragmentary and unclear. In the present study, the practical role of KLF10 in DEN-induced hepatic carcinogenesis, was elucidated using KLF10 null mice. In the necropsy and histopathological analysis, KLF10 KO mice exhibited lower tumor incidence and PCNA labeling indices than these values in the wild-type mice. Additional analyses revealed that the mRNA and protein levels of Smad3, TGF-beta 1, TGF-beta RI and p15 were increased in the tumor tissues of the KLF10 KO mice, while those of cMyc and cyclin D1 were downregulated. The level of phospho-Smad3 was also significantly higher in the tumor tissues of the KLF10 KO mice. All together, the KLF10 KO condition may reinforce the TGF-beta-Smad signaling pathway and confer tumor-suppressor effects against chemically induced liver tumorigenesis.
机译:肝癌是第三大常见癌症,并且肝癌的发病率和死亡率都在增加。肝肿瘤发生涉及许多信号传导途径。这些途径之一,即带有KLF10的转化生长因子-β(TGF-β)/ Smad途径,据报道在大多数情况下可抑制细胞增殖。但是,KLF10在各种病理生理条件下的实际功能仍然是零碎的,尚不清楚。在本研究中,使用KLF10无效小鼠阐明了KLF10在DEN诱导的肝癌发生中的实际作用。在尸检和组织病理学分析中,与野生型小鼠相比,KLF10 KO小鼠的肿瘤发生率和PCNA标记指数更低。进一步的分析表明,KLF10 KO小鼠的肿瘤组织中Smad3,TGF-β1,TGF-βRI和p15的mRNA和蛋白水平增加,而cMyc和cyclin D1的肿瘤组织被下调。在KLF10 KO小鼠的肿瘤组织中,磷酸化Smad3的水平也明显更高。总之,KLF10 KO条件可能会增强TGF-β-Smad信号传导途径,并赋予针对化学诱导的肝肿瘤发生的肿瘤抑制作用。

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