Abstract
BackgroundWith 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.MethodIn 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.ResultsWe 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.ConclusionOur 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.
Highlights
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
Immunohistochemistry staining showed that Grade 2 (G2) and S phase-expressed-1 (GTSE1) was mainly located in the cytoplasm of breast cancer cells (Fig. 2c), and its protein expression level was higher in Triple negative breast cancer (TNBC) (Fig. 2d), which was consistent with the result of the bc-GenExMiner database showing the GTSE1 mRNA level (Fig. 2e)
Since GTSE1 was the target gene of p53 [14], the expression level of GTSE1 was higher in the p53 mutated cell lines than that of wild type p53 cell line (Fig. 2f and g), and these results were confirmed by the results obtained from the Oncomine database (Fig. 2h)
Summary
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. The rapid development of high-throughput detection techniques has enabled the accumulation of tumor-related Omics data which are of great significance to study the mechanism of tumor progression [8, 9]. The management and mining of large quantities of biological data have become important in cancer research [10]. The TCGA database provides a large amount of tumor public data, which is widely used in tumor research, providing useful information for the discovery of new tumor biological indicators and drug targets [11, 12].
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