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Remarkably Reduced Expression of FoxO3a in Metaplastic Colorectum, Primary Colorectal Cancer and Liver Metastasis

ISSN号：1006-5725
期刊名称：《实用医学杂志》
时间：0
分类：Q939.139[生物学—微生物学] TQ463.5[化学工程—制药化工]
作者机构：[1]Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan 430030, China, [2]The Laboratory of Apoptosis and Cancer Biology, the State Key Laboratory of Biomembrane and Membrane Biotechnology,Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
相关基金：This project was supported by the grants from 973 Program Project from Ministry of Science and Technology in China （No. 2009CB521802）, and National Natural Science Foundation of China （No. 30872472, No. 30973496, and No. 30800569）.Acknowledgements We gratefully acknowledge Dr. Xiao-quan RAO and Dr. Li-shi SUN for their suggestions in cDNA Microarray and immunohistochemistry.

作者：何乐亚[1], 魏欣[1], 杜蕾[2], 刘鹭[1], 徐丰[1], 闵江[1], 李川[1], 陶德定[1], 陈佺[2], 胡俊波[1], 龚建平[1]

关键词：大肠癌, 原发性, 结直肠癌, RT-PCR, 肝, 微阵列分析, siRNA, 细胞核, FoxO3a, colorectal cancer, transcription factor, cell cycle arrest, target therapy

中文摘要：

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 G 2 -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.

英文摘要：

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 mi- cro-array analysis, which was confirmed by RT-PCR and Western blot in 28 patients. Moreover, immu- nohistochemistry （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 thera- peutic target in colorectal cancer.

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