BTB domain-containing 7 predicts low recurrence and suppresses tumor progression by deactivating Notch1 signaling in breast cancer
BTB domain-containing 7 predicts low recurrence and suppresses tumor progression by deactivating Notch1 signaling in breast cancer
复制标题
含有 BTB 结构域的 7 通过停用乳腺癌中的 Notch1 信号来预测低复发率并抑制肿瘤进展
DOI：
10.1007/s10549-020-05857-2
复制
发表时间：
2020-08-08
影响因子：
3.8
通讯作者：
Liu, Tian-Yu
中科院分区：
文献类型：
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作者：
Chen, Jian;Lai, Yuan-Hui;Liu, Tian-Yu
目的含BTB结构域7（BTBD7）基因调控上皮组织的重塑和分支器官的形成，并参与多种肿瘤的生物学行为。然而，它在乳腺癌中的作用尚未确定。本研究探讨了BTBD7在乳腺癌中的生物学作用和预后价值。方法我们使用GENT 2数据库鉴定BTBD 7的表达模式，并使用定量逆转录聚合酶链反应、蛋白质印迹和免疫组化评估其在乳腺癌组织和细胞系中的表达。我们对随访的121例乳腺癌病例队列进行了临床相关性和生存分析，并在Kaplan-Meier绘图仪中进行了验证。体外实验检测BTBD7对细胞增殖、侵袭和迁移的增益-损失效应。我们采用异种移植小鼠转移模型进行体内验证，并进行了乳腺癌10-通路报告基因阵列，蛋白质印迹，免疫荧光，细胞计数试剂盒-8，和transwell侵袭/迁移测定，以分析潜在的机制。结果BTBD7在人乳腺癌细胞系和组织中表达下调。BTBD7表达降低与阳性淋巴结状态、淋巴管浸润和TNM分期相关，而BTBD7高表达与乳腺癌低复发相关。BTBD7抑制乳腺癌中的细胞增殖、侵袭/迁移和肿瘤转移。研究的机制表明，BTBD 7的抑制作用是通过失活Notch 1信号在乳腺癌中。结论BTBD7抑制乳腺癌的进展，其高表达与乳腺癌的低复发相关。
Purpose BTB domain-containing 7 (BTBD7) has been found to regulate epithelial tissue remodeling and branched organ formation and has been reported to modulate the biological behavior of several cancers. However, its role in breast cancer has not been identified. This study investigated the biological role and prognostic value of BTBD7 in breast cancer. Methods We identified the BTBD7 expression pattern using the GENT2 database and assessed its expression in breast cancer tissue and cell lines using quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry. We conducted a clinical relevance and survival analysis on a cohort of 121 breast cancer cases from our follow-up and validated it in a Kaplan-Meier plotter. The gain-loss effect of BTBD7 on cell proliferation, invasion, and migration was detected in vitro. We employed a xenograft mouse metastatic model for in vivo validation and performed a Cignal Finder Cancer 10-Pathway Reporter Array, western blot, immunofluorescence, Cell Counting Kit-8, and transwell invasion/migration assays to analyze the potential mechanism. Results BTBD7 was downregulated in human breast cancer cell lines and tissues. Decreased BTBD7 expression correlated with a positive lymph node status, lymphovascular invasion, and TNM stage, while high BTBD7 expression correlated with low breast cancer recurrence. BTBD7 suppressed cell proliferation, invasion/migration, and tumor metastasis in breast cancer. The mechanism studied suggested that the inhibitory role of BTBD7 was through the deactivation of Notch1 signaling in breast cancer. Conclusion BTBD7 suppresses tumor progression, and its high expression correlates with low recurrence in breast cancer.