Restoration of TGF-beta signalling reduces tumorigenicity in human lung cancer cells.
Restoration of TGF-beta signalling reduces tumorigenicity in human lung cancer cells.
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DOI：
10.1038/sj.bjc.6602831
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发表时间：
2005-11-14
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
转化生长因子-β（TGF-β）家族的成员调节广泛的生物过程，包括细胞增殖、迁移、分化、凋亡和细胞外基质沉积。人肺癌中对TGF-β介导的肿瘤抑制功能的抵抗可能通过II型受体（TβRII）表达的丧失而发生。本研究采用RT-PCR和Western blot方法检测TβRII在人肺癌组织中的表达。我们用半定量RT-PCR检测了46例NSCLC中30例（65%）的TβRII表达下调。Western blot分析显示77%的病例TβRII表达减少。我们还确定了TβRII表达在肺腺癌细胞系（VMRC-LCD）中的作用，该细胞系由于缺乏TβRII表达而对TGF-β无反应。在这些细胞中稳定表达TβRII恢复TGF-β介导的效应，包括Smad 2/3和Smad 4复合物的形成，TGF-β应答报告基因的激活，细胞增殖抑制和凋亡增加。表达TβRII的克隆在软琼脂试验中显示集落形成减少，并且在无胸腺裸鼠中的致瘤性显著降低。因此，这些结果表明，通过稳定表达Tβ RII在TβRII缺失细胞中重建TGF-β信号传导可以逆转细胞的恶性行为，并且TβRII表达的缺失可能参与肺肿瘤的进展。
Members of the transforming growth factor-β (TGF-β) family regulate a wide range of biological processes including cell proliferation, migration, differentiation, apoptosis, and extracellular matrix deposition. Resistance to TGF-β-mediated tumour suppressor function in human lung cancer may occur through the loss of type II receptor (TβRII) expression. In this study, we investigated the expression pattern of TβRII in human lung cancer tissues by RT–PCR and Western blot analyses. We observed downregulation of TβRII in 30 out of 46 NSCLC samples (65%) by semiquantitative RT–PCR. Western blot analyses with tumour lysates showed reduced expression of TβRII in 77% cases. We also determined the effect of TβRII expression in lung adenocarcinoma cell line (VMRC-LCD) that is not responsive to TGF-β due to lack of TβRII expression. Stable expression of TβRII in these cells restored TGF-β-mediated effects including Smad2/3 and Smad4 complex formation, TGF-β-responsive reporter gene activation, inhibition of cell proliferation and increased apoptosis. Clones expressing TβRII showed reduced colony formation in soft-agarose assay and significantly reduced tumorigenicity in athymic nude mice. Therefore, these results suggest that reestablishment of TGF-β signalling in TβRII null cells by stable expression of TβRII can reverse malignant behaviour of cells and loss of TβRII expression may be involved in lung tumour progression.
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影响因子：
10.5
作者：
Hata, A;Lagna, G;Hemmati-Brivanlou, A
通讯作者：
Hemmati-Brivanlou, A
人类小细胞肺癌细胞系中转化生长因子II型受体的失活。
影响因子：
8.8
作者：
Hougaard, S;Norgaard, P;Abrahamsen, N;Moses, HL;Spang-Thomsen, M;Poulsen, HS
通讯作者：
Poulsen, HS
DOI：
10.1073/pnas.98.3.992
发表时间：
2001-01-30
影响因子：
11.1
作者：
Chen, CR;Kang, YB;Massagué, J
通讯作者：
Massagué, J
影响因子：
4.8
作者：
Halder, SK;Beauchamp, RD;Datta, PK
通讯作者：
Datta, PK
影响因子：
4.8
作者：
Ishisaki, A;Yamato, K;Nishihara, T
通讯作者：
Nishihara, T