TGF-β1 induces HMGA1 expression in human breast cancer cells: implications of the involvement of HMGA1 in TGF-β signaling.
TGF-β1 induces HMGA1 expression in human breast cancer cells: implications of the involvement of HMGA1 in TGF-β signaling.
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TGF-β 1 诱导人乳腺癌细胞中 HMGA1 表达：HMGA1 参与 TGF-β 信号转导的意义
DOI：
10.3892/ijmm.2015.2062
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发表时间：
2015-03
影响因子：
5.4
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Zu X;Zhong J;Tan J;Tan L;Yang D;Zhang Q;Ding W;Liu W;Wen G;Liu J;Cao R;Jiang Y
转化生长因子-β-1信号转导通路和高迁移率族蛋白A(HMGA1)通过诱导上皮-间充质转化，在乳腺癌的发生发展过程中发挥重要作用。然而，转化生长因子-β-1和HMGA1在乳腺癌细胞中的相关性还不是很清楚。在这项研究中，我们确定了转化生长因子-β1对乳腺癌细胞HMGA1表达的影响，并探讨了HMGA1在乳腺癌进展中的作用。RT-qPCR和免疫荧光染色结果显示，转化生长因子-β1可诱导乳腺癌细胞HMGA的表达，但磷脂酰肌醇-3激酶(PI3K)信号抑制剂可阻断转化生长因子-β1诱导的HMGA的表达。荧光素酶活性分析表明，特异性蛋白1(Sp1)参与了转化生长因子-β1诱导的HMGA1启动子活性的调节。此外，通过HMGA1启动子的转染增强了HMGA1的表达，包括增殖、迁移和侵袭，组织芯片显示表达人表皮生长因子受体2(HER2)的乳腺肿瘤显示HMGA1的表达水平更高(P=0.007)。此外，导管癌组织中HMGA1的表达水平也高于小叶乳腺癌组织(P=0.000)。这些发现建立了HMGA1和转化生长因子-β1在乳腺癌中的第一个联系，为HMGA1在乳腺癌进展中的关键作用提供了进一步的证据。
Transforming growth factor-β1 (TGF-β1) signaling and high mobility group A (HMGA1) are known to play essential roles in the progression of breast cancer by inducing epithelial-mesenchymal transition. However, the correlation between TGF-β1 and HMGA1 in breast cancer cell is not yet well understood. In this study, we determined the effects of TGF-β1 on HMGA1 expression in breast cancer cells and examined the role of HMGA1 in breast cancer progression. Our results demonstrated that TGF-β1 induced the expression of HMGA1 in both MCF-7 and MDA-MB-231 breast cancer cells, as shown by RT-qPCR and immunofluorescence staining; however, the TGF-β1-induced expression of HMGA was blocked by treatment of the cells with phosphatidylinositol-3 kinase (PI3K) signaling inhibitors. Moreover, the HMGA1 promoter activity was found to be activated by TGF-β1 in the MCF-7 and MDA-MB-231 cells and we found that specificity protein 1 (Sp1) was involved in the TGF-β1-induced HMGA1 promoter activity, as shown by luciferase activity assay. Furthermore, the enforced expression of HMGA1 by transfection with a HMGA1 promoter enhanced cellular oncogenic properties, including proliferation, migration and invasion, and a tissue microarray revealed that breast tumors expressing human epidermal growth factor receptor 2 (HER2) showed higher expression levels of HMGA1 (P=0.007). In addition, higher HMGA1 expression levels were also observed in the ductal breast cancer cases compared with the lobular breast cancer cases (P=0.000). These findings establish the first link between HMGA1 and TGF-β1 in breast cancer, providing further evidence of the pivotal role of HMGA1 in breast cancer progression.
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影响因子：
11.2
作者：
Resar LM
通讯作者：
Resar LM
影响因子：
11.5
作者：
Chiappetta, G;Botti, G;Fusco, A
通讯作者：
Fusco, A
影响因子：
1.4
作者：
Rho, Young Soo;Lim, Young Chang;Shin, Hyung Sik
通讯作者：
Shin, Hyung Sik
影响因子：
4.4
作者：
Schuldenfrei A;Belton A;Kowalski J;Talbot CC Jr;Di Cello F;Poh W;Tsai HL;Shah SN;Huso TH;Huso DL;Resar LM
通讯作者：
Resar LM
影响因子：
2
作者：
Flohr, AM;Rogalla, P;Bullerdiek, J
通讯作者：
Bullerdiek, J