PGC-1β cooperating with FOXA2 inhibits proliferation and migration of breast cancer cells
PGC-1β cooperating with FOXA2 inhibits proliferation and migration of breast cancer cells
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PGC-1β协同FOXA2抑制乳腺癌细胞增殖和迁移
DOI：
10.1186/s12935-019-0810-5
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发表时间：
2019-04-11
影响因子：
5.8
通讯作者：
Wang, Libin
中科院分区：
文献类型：
--
作者：
Cao, Jia;Wang, Xi;Wang, Libin
背景：在全球癌症发病率统计中，乳腺癌是女性最常见的恶性肿瘤之一。过氧酶体-γ共激活因子-1β(PGC-1β)长期以来一直被认为与这种类型的肿瘤发生有关。然而，PGC-1β在人乳腺癌中的作用机制尚不完全清楚，其功能还有待进一步阐明。方法：采用定量逆转录聚合酶链式反应和Western blotting方法分别检测乳腺癌组织和细胞系中PGC-1β和FOXA2的mRNA和蛋白表达。为了进一步显示PGC-1β和FOXA2的表达和定位，采用免疫组织化学和免疫荧光染色方法。体外稳定表达PGC-1β和FOXA2后，通过CCK8实验、克隆形成实验、Transwell实验和伤口愈合实验评价PGC-1β和FOXA2对细胞增殖和迁移的影响。采用裸鼠移植瘤模型评价肿瘤的体内生长情况。结果：PGC-1β在乳腺癌组织和细胞系中表达上调，FOXA2表达下调。这两种蛋白质可以相互作用形成复合体。此外，我们还发现，PGC-1β干扰和FOXA2过表达的组合在体外显著抑制了细胞的增殖和迁移，以及体内的肿瘤生长。我们进一步证实PGC-1β和FOXA2与PI3K-AKT-mTOR信号通路密切相关，并通过激活PI3K-AKT-mTOR信号通路发挥其生物学功能。结论：PGC-1β的下调和FOXA2的过表达通过调节PI3K-AKT-mTOR信号通路而明显抑制乳腺癌细胞的功能。
Background: Breast cancer is one of the most common malignancy among females from the worldwide cancer incidence statistics. Peroxisome gamma coactivator-1 beta (PGC-1 beta) has long been identified to be involved in this type of tumorigenesis. However, the mechanisms of PGC-1 beta in human breast cancer have not been fully understood and the function requires to be further elucidated.Methods: mRNA and protein expression of PGC-1 beta and FOXA2 in breast cancer tissues and cell lines were determined by qRT-PCR and Western Blotting, respectively. To further visualize the expression and localization of PGC-1 beta and FOXA2, immunochemistry and immunofluorescence staining methods were employed. The effect of PGC-1 beta and FOXA2 on cell proliferation and migration were evaluated by CCK8, clone formation, transwell and wound-healing assays, which has been done either with stable PGC-1 beta knockdown or FOXA2 overexpression in vitro. Xenografts model of nude mice were used to evaluate tumor growth in vivo. In addition, proteins expression of the PI3K-AKT-mTOR signaling pathway involved in the regulation of breast cancer were detected by Western Blotting.Results: Our results showed that PGC-1 beta was upregulated and FOXA2 was downregulated in breast cancer tissues and cell lines. These two proteins can be interacted with each other to form the complex. Also, we found the combination of PGC-1 beta interference with FOXA2 overexpression significantly inhibited cell proliferation and migration in vitro as well as tumor growth in vivo. We further identified that PGC-1 beta and FOXA2 strongly correlated with the PI3K-AKT-mTOR signaling pathway, and they exerted their biological functions by activating this pathway.Conclusions: We demonstrated that downregulation of PGC-1 beta combined with overexpression of FOXA2 obviously inhibited the function of breast cancer cells through regulating the PI3K-AKT-mTOR pathway.