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

作　　者：何乐亚 魏欣 杜蕾 刘鹭 徐丰 闵江 李川 陶德定 陈佺 胡俊波 龚建平 

机构地区：[1]Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology [2]The Laboratory of Apoptosis and Cancer Biology, the State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2013年第2期205-211,共7页华中科技大学学报（医学英德文版）

基　　金：supported by the grants from 973 Program Project from Ministry of Science and Technology in China(No.2009CB521802);National Natural Science Foundation of China(No.30872472,No.30973496,and No.30800569)

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.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.

关 键 词：FOXO3A colorectal cancer transcription factor cell cycle arrest target therapy 

分 类 号：R735[医药卫生—肿瘤]