TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells.
TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells.
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DOI：
10.1111/cas.12355
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发表时间：
2014-03
期刊：
影响因子：
5.7
通讯作者：
Kato M
中科院分区：
文献类型：
--
作者：
Vo Nguyen TT;Watanabe Y;Shiba A;Noguchi M;Itoh S;Kato M
TMEPAI/PMEPA 1是一种跨膜蛋白，最初被鉴定为前列腺RNA，其合成由睾酮或其衍生物诱导。TMEPAI是转化生长因子-β（TGF-β）/Smad信号转导的直接靶基因，参与TGF-β/Smad信号转导持续时间和强度的负反馈调控。TMEPAI在许多类型的癌症中组成性地高度表达，并且与不良预后相关。在这里，我们报告TMEPAI在肺腺癌细胞系Calu 3、NCI-H23和RERF-LC-KJ中高度表达。TGF-β受体激酶拮抗剂SB 208和TGF-β中和抗体显著抑制了这些癌细胞中TMEPAI的表达。这些结果表明，TMEPAI在这些癌细胞中的组成型表达依赖于自分泌TGF-β刺激。在存在TGF-β的情况下，Calu 3和NCI-H23细胞中TMEPAI的敲低增强了Smad 2磷酸化水平并显著抑制了细胞增殖，表明高表达的TMEPAI抑制了这些癌细胞中Smad磷酸化水平并降低了TGF-β/Smad信号传导的生长抑制作用。此外，Calu 3和NCI-H23细胞中TMEPAI的敲低抑制体外球体形成和皮下肿瘤形成。在NOD-SCID小鼠中体内尾静脉注射后，在组织和肺中。总之，这些实验表明TMEPAI促进肺癌细胞中的致瘤活性。
TMEPAI/PMEPA1 is a transmembrane protein that was originally identified as a prostatic RNA, the synthesis of which is induced by testosterone or its derivatives. We have recently identified TMEPAI as a direct target gene of transforming growth factor-β (TGF-β)/Smad signaling that participates in negative feedback control of the duration and intensity of TGF-β/Smad signaling. TMEPAI is constitutively and highly expressed in many types of cancer and is associated with poor prognosis. Here, we report that TMEPAI is highly expressed in the lung adenocarcinoma cell lines Calu3, NCI-H23, and RERF-LC-KJ. Expression of TMEPAI in these cancer cells was significantly suppressed by a TGF-β receptor kinase antagonist, SB208, and by TGF-β neutralizing antibodies. These results suggest that constitutive expression of TMEPAI in these cancer cells depends on autocrine TGF-β stimulation. Knockdown of TMEPAI in Calu3 and NCI-H23 cells enhanced levels of Smad2 phosphorylation and significantly suppressed cell proliferation in the presence of TGF-β, indicating that highly expressed TMEPAI suppresses levels of Smad phosphorylation in these cancer cells and reduces the growth inhibitory effects of TGF-β/Smad signaling. Furthermore, knockdown of TMEPAI in Calu3 and NCI-H23 cells suppressed sphere formation in vitro and tumor formation in s.c. tissues and in lungs after tail vein injection in NOD-SCID mice in vivo. Together, these experiments indicate that TMEPAI promotes tumorigenic activities in lung cancer cells.
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影响因子：
5.8
作者：
Rajkumar T;Vijayalakshmi N;Gopal G;Sabitha K;Shirley S;Raja UM;Ramakrishnan SA
通讯作者：
Ramakrishnan SA
DOI：
10.1073/pnas.0909797107
发表时间：
2010-02-02
影响因子：
11.1
作者：
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通讯作者：
Fitzgerald, Rebecca C.
影响因子：
11.2
作者：
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通讯作者：
Grady, William M.
影响因子：
7.5
作者：
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通讯作者：
ten Dijke, Peter
影响因子：
7.3
作者：
Liu, Rong;Zhou, Zhongmei;Chen, Ceshi
通讯作者：
Chen, Ceshi