Department of General Surgery, Heze Municipal Hospital, Caozhou Road, Heze, 274000, Shandong, China.
Department of Oncology, Heze Municipal Hospital, Caozhou Road, Heze, 274000, Shandong, China.
Mol Med. 2020 Apr 9;26(1):33. doi: 10.1186/s10020-020-00161-7.
The present study aims to investigate the effects of pituitary tumor transforming gene (PTTG) 1 on breast cancer and its underlying mechanism.
GEO data set was applied to analyze the relationship between PTTG1 and survival status and the TCGA breast cancer dataset was used to explore its possible targets. The stable cell lines including PTTG1 knockdown cells, estrogen receptor (ESR) 1 knockdown cells, and PTTG1 overexpression cells were constructed. MTT was used to determine cell viabilities. Propidium iodide (PI) staining and flow cytometry were used to analyze the cell cycle. Quantitative polymerase chain reaction (qPCR) was employed to determine the mRNA expressions. Points mutations and luciferase reporter assays were used to determine the binding sites of estrogen.
PTTG1 was associated with poor survival rates in breast cancer. In vitro study demonstrated that PTTG1 affected cell viabilities of MCF7 and T47D cells. Besides, PTTG1 affected cell cycle arrest of breast cancer cells. Overexpression of PTTG1 led to more breast cancer cells distributed in S phase. The levels of PTTG1 were associated with estrogen and further results showed that the levels of PTTG1 were positively correlated to tamoxifen resistance. Two genes including CCNA2 and CCNB2 were identified to be possible targets of PTTG1.
Estrogen-regulated PTTG1 promotes the development of breast cancer cells by the regulation of the cell cycle.
本研究旨在探讨垂体瘤转化基因（PTTG1）对乳腺癌的影响及其潜在机制。
采用 GEO 数据集分析 PTTG1 与生存状态的关系，并利用 TCGA 乳腺癌数据集探讨其可能的靶点。构建包括 PTTG1 敲低细胞、雌激素受体（ESR）1 敲低细胞和 PTTG1 过表达细胞的稳定细胞系。MTT 法测定细胞活力。碘化丙啶（PI）染色和流式细胞术分析细胞周期。定量聚合酶链反应（qPCR）测定 mRNA 表达。点突变和荧光素酶报告基因检测用于确定雌激素的结合位点。
PTTG1 与乳腺癌患者的生存率降低有关。体外研究表明，PTTG1 影响 MCF7 和 T47D 细胞的细胞活力。此外，PTTG1 影响乳腺癌细胞的细胞周期停滞。PTTG1 的过表达导致更多的乳腺癌细胞分布在 S 期。PTTG1 的水平与雌激素有关，进一步的结果表明，PTTG1 的水平与他莫昔芬耐药呈正相关。鉴定出两个可能的 PTTG1 靶点基因，包括 CCNA2 和 CCNB2。
雌激素调控的 PTTG1 通过调节细胞周期促进乳腺癌细胞的发展。
