Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer.
Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer.
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DOI：
10.1002/mc.21852
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发表时间：
2013-04
影响因子：
4.6
通讯作者：
Ko, Tien C.
中科院分区：
文献类型：
--
作者：
Deng, Xiyun;Cao, Yanna;Liu, Yan;Li, Fazhi;Sambandam, Kamalanathan;Rajaraman, Srinivasan;Perkins, Archibald S.;Fields, Alan P.;Hellmich, Mark R.;Townsend, Courtney M., Jr.;Thompson, E. Aubrey;Ko, Tien C.
关键词：
人结直肠癌（CRC）细胞对转化生长因子-β (TGF-β)的抗增殖作用具有抗性，提示TGF-β信号的破坏在结直肠癌的发生中起重要作用。生态亲和性病毒整合位点-1 （Evi-1）癌蛋白通过与Smads相互作用抑制TGF-β信号，但其在结直肠癌中的作用尚未确定。本研究的目的是确定Evi-1是否在CRCs中发挥作用，并表征Evi-1在CRCs中的转录物。Evi-1在53%的人类结直肠癌样本、100%的结肠腺瘤样本和100%的人类结肠癌细胞系中过表达。利用5 ' RACE技术，我们从人结直肠癌组织中克隆了一个新的Evi-1转录本（Evi-1e），发现该转录本在结直肠癌组织中的表达水平高于正常组织，是结直肠癌中主要的Evi-1转录本。短暂转染Evi-1可抑制TGF-β诱导的转录活性，逆转TGF-β对MC-26小鼠结肠癌细胞的生长抑制作用。总之，我们已经确定了Evi-1癌蛋白的过表达是一种新的机制，通过这种机制，人类crc的一个子集可以逃避TGF-β的调节。我们还发现了一种新的Evi-1转录本Evi-1e，作为人类crc中表达的主要Evi-1转录本。
Human colorectal cancer (CRC) cells are resistant to the anti-proliferative effect of transforming growth factor-β (TGF-β), suggesting that disruption of TGF-β signaling plays an important role in colorectal carcinogenesis. Ecotropic virus integration site-1 (Evi-1) oncoprotein represses TGF-β signaling by interacting with Smads, but its role in CRC has not been established. The purpose of this study is to determine whether Evi-1 plays role(s) in CRCs and to characterize Evi-1 transcript(s) in CRCs. Evi-1 was overexpressed in 53% of human CRC samples, 100% of colon adenoma samples, and 100% of human colon cancer cell lines tested. Using 5′ RACE, we cloned a novel Evi-1 transcript (Evi-1e) from a human CRC tissue and found that this novel transcript was expressed at a higher level in CRC tissues than in normal tissues and was the major Evi-1 transcript in CRCs. Transient Evi-1 transfection inhibited TGF-β-induced transcriptional activity and reversed the growth inhibitory effect of TGF-β in MC-26 mouse colon cancer cells. In conclusion, we have identified overexpression of Evi-1 oncoprotein as a novel mechanism by which a subset of human CRCs may escape TGF-β regulation. We have also identified a novel Evi-1 transcript, Evi-1e, as the major Evi-1 transcript expressed in human CRCs.
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影响因子：
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