State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Guangdong Medical University, Zhanjiang, 524023, People's Republic of China.
J Exp Clin Cancer Res. 2019 Apr 8;38(1):152. doi: 10.1186/s13046-019-1157-4.
With the rapid development of the high throughput detection techniques, tumor-related Omics data has become an important source for studying the mechanism of tumor progression including breast cancer, one of the major malignancies worldwide. A previous study has shown that the G2 and S phase-expressed-1 (GTSE1) can act as an oncogene in several human cancers. However, its functional roles in breast cancer remain elusive.
In this study, we analyzed breast cancer data downloaded from The Cancer Genome Atlas (TCGA) databases and other online database including the Oncomine, bc-GenExMiner and PROGgeneV2 database to identify the molecules contributing to the progression of breast cancer. The GTSE1 expression levels were investigated using qRT-PCR, immunoblotting and IHC. The biological function of GTSE1 in the growth, migration and invasion of breast cancer was examined in MDA-MB-231, MDA-MB-468 and MCF7 cell lines. The in vitro cell proliferative, migratory and invasive abilities were evaluated by MTS, colony formation and transwell assay, respectively. The role of GTSE1 in the growth and metastasis of breast cancer were revealed by in vivo investigation using BALB/c nude mice.
We showed that the expression level of GTSE1 was upregulated in breast cancer specimens and cell lines, especially in triple negative breast cancer (TNBC) and p53 mutated breast cancer cell lines. Importantly, high GTSE1 expression was positively correlated with histological grade and poor survival. We demonstrated that GTSE1 could promote breast cancer cell growth by activating the AKT pathway and enhance metastasis by regulating the Epithelial-Mesenchymal transition (EMT) pathway. Furthermore, it could cause multidrug resistance in breast cancer cells. Interestingly, we found that GTSE1 could regulate the p53 function to alter the cell cycle distribution dependent on the mutation state of p53.
Our results reveal that GTSE1 played a key role in the progression of breast cancer, indicating that GTSE1 could serve as a novel biomarker to aid in the assessment of the prognosis of breast cancer.
随着高通量检测技术的快速发展，肿瘤相关的组学数据已成为研究肿瘤进展机制的重要来源，包括乳腺癌，这是全球主要恶性肿瘤之一。先前的研究表明，G2 和 S 期表达的 1（GTSE1）在几种人类癌症中可以作为癌基因发挥作用。然而，其在乳腺癌中的功能作用仍不清楚。
在这项研究中，我们分析了从癌症基因组图谱（TCGA）数据库以及 Oncomine、bc-GenExMiner 和 PROGgeneV2 等在线数据库下载的乳腺癌数据，以确定促进乳腺癌进展的分子。使用 qRT-PCR、免疫印迹和 IHC 检测 GTSE1 的表达水平。在 MDA-MB-231、MDA-MB-468 和 MCF7 细胞系中研究 GTSE1 在乳腺癌生长、迁移和侵袭中的生物学功能。通过 MTS、集落形成和 Transwell 分析分别评估体外细胞增殖、迁移和侵袭能力。通过 BALB/c 裸鼠体内研究揭示了 GTSE1 在乳腺癌生长和转移中的作用。
我们发现 GTSE1 的表达水平在乳腺癌标本和细胞系中上调，尤其是在三阴性乳腺癌（TNBC）和 p53 突变的乳腺癌细胞系中。重要的是，高 GTSE1 表达与组织学分级和不良预后呈正相关。我们证明 GTSE1 可以通过激活 AKT 通路促进乳腺癌细胞生长，并通过调节上皮-间充质转化（EMT）通路增强转移。此外，它可以导致乳腺癌细胞的多药耐药。有趣的是，我们发现 GTSE1 可以调节 p53 的功能，根据 p53 的突变状态改变细胞周期分布。
我们的结果表明 GTSE1 在乳腺癌的进展中发挥了关键作用，表明 GTSE1 可以作为一种新的生物标志物，有助于评估乳腺癌的预后。
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