Remarkably reduced expression of FoxO3a in metaplastic colorectum, primary colorectal cancer and liver metastasis

Remarkably reduced expression of FoxO3a in metaplastic colorectum, primary colorectal cancer and liver metastasis
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FoxO3a在化生性结直肠癌、原发性结直肠癌和肝转移中的表达显着降低

DOI:
10.1007/s11596-013-1098-7
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发表时间:
2013-04-01
影响因子:
--
通讯作者:
Gong, Jian-ping
Gong, Jian-ping
中科院分区:
生物4区
文献类型:
--
作者:
He, Le-ya;Wei, Xin;Gong, Jian-ping

文献摘要

被引文献

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叉头转录因子家族成员(FoxOs)被认为是潜在的肿瘤相关药物靶点,因此最近被大量研究。在本研究中,FoxO 3a,该家族的一个主要成员,被确定为下调,在大肠癌通过微阵列分析,这是通过RT-PCR和Western blot证实在28例患者。免疫组化(IHC)结果显示,FoxO 3a在99例原发性结直肠癌、肝转移灶、甚至化生性结直肠组织中的表达均明显降低。免疫组化还显示FoxO 3a从肿瘤相关组织的大多数细胞的细胞核中被排除。通过siRNA沉默FoxO 3a导致G2-M期细胞升高。我们的结论是,下调FoxO 3a可能大大有助于肿瘤的发展,因此FoxO 3a可能代表一个新的治疗靶点在结直肠癌。
The forkhead family members of transcription factors (FoxOs) are expected to be potential cancer-related drug targets and thus are being extremely studied recently. In the present study, FoxO3a, one major member of this family, was identified to be down-regulated in colorectal cancer through micro-array analysis, which was confirmed by RT-PCR and Western blot in 28 patients. Moreover, immunohistochemistry (IHC) showed that the expression levels of FoxO3a were remarkably reduced in 99 cases of primary colorectal cancer, liver metastasis, and even in metaplastic colorectal tissue. IHC also revealed an exclusion of FoxO3a from the nucleus of most cells of tumor-associated tissues. Silencing FoxO3a by siRNA led to elevation of G2-M phase cells. We conclude that the downregulation of FoxO3a may greatly contribute to tumor development, and thus FoxO3a may represent a novel therapeutic target in colorectal cancer.