Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice.
Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice.
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DOI：
10.1038/onc.2011.41
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发表时间：
2011-07-21
期刊：
影响因子：
8
通讯作者：
Rio, M. C.
中科院分区：
文献类型：
--
作者：
Buache, E.;Etique, N.;Alpy, F.;Stoll, I.;Muckensturm, M.;Reina-San-Martin, B.;Chenard, M. P.;Tomasetto, C.;Rio, M. C.
关键词：
虽然三叶因子1 （TFF1，以前称为pS2）在约50%的人类乳腺肿瘤中异常表达，但其在该疾病中的生理病理作用研究甚少。此外，也报道了有争议的数据。因此，TFF1在乳腺中的功能需要明确。在这项研究中，我们使用逆转录病毒载体，在四种人乳腺上皮细胞系中进行了TFF1功能增加或丧失的实验：正常永生化TFF1阴性MCF10A，恶性TFF1阴性MDA-MB-231和恶性TFF1阳性MCF7和ZR75.1。TFF1的表达刺激了四种细胞系的迁移和侵袭。在MCF10A、MDA-MB-231和MCF7细胞中强制表达TFF1并不会改变锚定依赖性或非依赖性细胞的增殖。相比之下，MCF7中TFF1的敲低增强了软琼脂集落的形成。在裸鼠体内实验中证实，在缺乏TFF1的情况下，MCF7细胞的致癌潜力增加。此外，与野生型小鼠相比，化学诱导的tff1缺陷小鼠（TFF1-KO）的肿瘤发生导致乳腺肿瘤发生率更高，肿瘤大小更大。同样，TFF1-KO的卵巢和肺部肿瘤的发展也增加了。总的来说，我们的结果清楚地表明，TFF1不表现出致癌特性，而是减少肿瘤的发展。TFF1的这种有益功能与许多临床研究一致，这些研究报告了TFF1阳性乳腺原发性肿瘤患者的更好预后。
Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover, controversial data have been reported. TFF1 function in the mammary gland therefore needs to be clarified. In this study, using retroviral vectors, we performed TFF1 gain- or loss-of-function experiments in four human mammary epithelial cell lines: normal immortalized TFF1-negative MCF10A, malignant TFF1-negative MDA-MB-231 and malignant TFF1-positive MCF7 and ZR75.1. The expression of TFF1 stimulated the migration and invasion in the four cell lines. Forced TFF1 expression in MCF10A, MDA-MB-231 and MCF7 cells did not modify anchorage-dependent or -independent cell proliferation. By contrast, TFF1 knockdown in MCF7 enhanced soft-agar colony formation. This increased oncogenic potential of MCF7 cells in the absence of TFF1 was confirmed in vivo in nude mice. Moreover, chemically induced tumorigenesis in TFF1-deficient (TFF1-KO) mice led to higher tumor incidence in the mammary gland and larger tumor size compared with wild-type mice. Similarly, tumor development was increased in the TFF1-KO ovary and lung. Collectively, our results clearly show that TFF1 does not exhibit oncogenic properties, but rather reduces tumor development. This beneficial function of TFF1 is in agreement with many clinical studies reporting a better outcome for patients with TFF1-positive breast primary tumors.
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DOI：
10.1186/bcr1639
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
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DOI：
10.1083/jcb200108056
发表时间：
2002-05-27
期刊：
The Journal of cell biology
影响因子：
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作者：
Bossenmeyer-Pourié C;Kannan R;Ribieras S;Wendling C;Stoll I;Thim L;Tomasetto C;Rio MC
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Rio MC