Reduction in Smad2/3 signaling enhances tumorigenesis but suppresses metastasis of breast cancer cell lines.
Reduction in Smad2/3 signaling enhances tumorigenesis but suppresses metastasis of breast cancer cell lines.
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发表时间：
2003-12
期刊：
影响因子：
11.2
通讯作者：
F. Tian;S. Dacosta Byfield;W. Parks;S. Yoo;A. Felici;Binwu Tang;E. Piek;L. Wakefield;A. Roberts
中科院分区：
文献类型：
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作者：
F. Tian;S. Dacosta Byfield;W. Parks;S. Yoo;A. Felici;Binwu Tang;E. Piek;L. Wakefield;A. Roberts
转化生长因子β在乳腺癌中的作用是有争议的，其抑癌和促癌活性已被证实。为了解决是否相同或不同的信号转导通路介导这些相反的活动，我们操纵Smad 2/3信号通路的细胞来源相同，但不同程度的恶性肿瘤来源于MCF 10A人乳腺细胞。我们发现，干扰内源性Smad 2/3信号增强了恶性肿瘤前和分化良好的肿瘤细胞的异种移植肿瘤的恶性程度，但强烈抑制肺转移的更具侵略性的癌细胞后，尾静脉注射。Smad 3在相同细胞中的过表达具有相反的效果。这些数据表明，Smad 2/3信号通路介导肿瘤抑制和促转移信号，这取决于细胞环境。
The role of transforming growth factor beta in breast cancer is controversial with tumor suppressor and pro-oncogenic activities having been demonstrated. To address whether the same or different signal transduction pathways mediate these opposing activities, we manipulated the Smad2/3 signaling pathway in cells of common origin but differing degrees of malignancy derived from MCF10A human breast cells. We show that interference with endogenous Smad2/3 signaling enhances the malignancy of xenografted tumors of premalignant and well-differentiated tumor cells but strongly suppresses lung metastases of more aggressive carcinoma cells after tail vein injection. Overexpression of Smad3 in the same cells has opposite effects. The data demonstrate that the Smad2/3 signaling pathway mediates tumor suppressor and prometastatic signals, depending on the cellular context.