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首页> 外文期刊>Cancer biology & therapy >Cables1 is a tumor suppressor gene that regulates intestinal tumor progression in ApcMin mice
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Cables1 is a tumor suppressor gene that regulates intestinal tumor progression in ApcMin mice

机译：Cables1是一种肿瘤抑制基因，可调节ApcMin小鼠的肠道肿瘤进展

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The transformation of colonic mucosal epithelium to adenocarcinoma requires progressive oncogene activation and tumor suppressor gene inactivation. Loss of chromosome 18q is common in colon cancer but not in precancerous adenomas. A few candidate tumor suppressor genes have been identified in this region, including CABLES1 at 18q11.2-12.1. This study investigates the role of CABLES1 in an in vivo mouse model of intestinal adenocarcinoma and in human colon cancer cell culture. ApcMin/+ mice were crossed with mice harboring targeted inactivation of the Cables1 gene (Cables1-/-). The intestinal tumor burden and tumor expression of β-catenin and PCNA was compared in Cables1+/+ApcMin/+ and Cables1 -/-ApcMin/+ mice. β-catenin activity in human colon cancer cells with CABLES1 inactivation and intestinal progenitor cell function in Cables1-/- mice were assayed in vitro. The mean number of small intestinal tumors per mouse was 3.1 ± 0.6 in Cables1+/+ ApcMin/+ mice, compared with 32.4 ± 3.5 in the Cables1 -/-ApcMin/+ mice (P 0.0001). Fewer colonic tumors were observed in Cables1+/+ApcMin/+ mice (mean 0.6 ± 0.1) compared with the Cables1-/-ApcMin/+ mice (mean 1.3 ± 0.3, P = 0.01). Tumors from Cables1-/-Apc Min/+ mice demonstrated increased nuclear expression of β-catenin and an increased number of PCNA-positive cells. In vitro studies revealed that CABLES1 deficiency increased β-catenin dependent transcription and increased intestinal progenitor cell activity. Loss of Cables1 enhances tumor progression in the ApcMin/+ mouse model and activates the Wnt/β-catenin signaling pathway. Cables1 is a tumor suppressor gene on chromosome 18q in this in vivo mouse model and likely has a similar role in human colon cancer.
机译：结肠粘膜上皮向腺癌的转化需要渐进的癌基因激活和肿瘤抑制基因失活。 18q染色体丢失在结肠癌中很常见，但在癌前腺瘤中并不常见。在该区域已鉴定出一些候选肿瘤抑制基因，包括18q11.2-12.1处的CABLES1。这项研究调查了CABLES1在肠道腺癌的体内小鼠模型和人类结肠癌细胞培养中的作用。 ApcMin / +小鼠与携带Cables1基因（Cables1-/-）靶向失活的小鼠杂交。比较了Cables1 + / + ApcMin / +和Cables1 //-ApcMin / +小鼠的肠道肿瘤负荷和β-catenin和PCNA的表达。在体外测定了CableS1失活的人结肠癌细胞中β-catenin的活性以及Cables1-/-小鼠的肠道祖细胞功能。每只小鼠的小肠肿瘤平均数在Cables1 + / + ApcMin / +小鼠中为3.1±0.6，而在Cables1-/-ApcMin / +小鼠中为32.4±3.5（P <0.0001）。与Cables1-/-ApcMin / +小鼠（平均值1.3±0.3，P = 0.01）相比，Cables1 + / + ApcMin / +小鼠（平均0.6±0.1）中观察到的结肠肿瘤更少。来自Cables1 //-Apc Min / +小鼠的肿瘤显示β-catenin的核表达增加，PCNA阳性细胞增加。体外研究表明，CABLES1缺乏症增加了β-catenin依赖性转录并增加了肠道祖细胞的活性。 Cables1的缺失会增强ApcMin / +小鼠模型中的肿瘤进展并激活Wnt /β-catenin信号通路。 Cables1在此体内小鼠模型中是染色体18q上的抑癌基因，可能在人类结肠癌中具有相似的作用。

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