Loss of BTG2 expression in breast cancer progression

乳腺癌进展过程中 BTG2 表达缺失

• 批准号: 23591906
• 负责人: TAKAHASHI Fumiyuki
• 金额: $ 3.33万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591906/
• 关键词: 乳癌; BTG2; 転移; 上皮間葉転換; Lapatinib; EMT; 幹細胞; microRNA

EMT plays an important role in the tumor invasion and metastases. In human breast cancer, decreased BTG2 expression correlates with metastatic recurrence and decrease in overall survival, suggesting that suppression of BTG2 plays a critical role in disease progression. To analyze the role of BTG2 in breast cancer, BTG2 expression was knocked down in mammary epithelial cells. Suppression of BTG2 enhanced the motility of cells in vitro and enhanced tumor growth and metastasis in vivo. The effects of BTG2 knockdown were mediated through activation of HER2 and HER3, leading to elevated AKT phosphorylation. Suppression of HER activation using the lapatinib abrogated the effects of BTG2 knockdown, including the increased cell migration observed in vitro and the enhancement of tumorigenesis and metastasis in vivo. These results link BTG2-dependent effects on tumor progression, and raise the possibility that targeted inhibition of this pathway may be relevant in treatment breast cancers.

EMT在肿瘤的侵袭和转移中发挥着重要作用。在人类乳腺癌中，BTG2 表达下降与转移复发和总生存率下降相关，表明 BTG2 的抑制在疾病进展中发挥着关键作用。为了分析 BTG2 在乳腺癌中的作用，我们在乳腺上皮细胞中敲低了 BTG2 的表达。 BTG2的抑制增强了体外细胞的运动性并增强了体内肿瘤的生长和转移。 BTG2 敲低的作用是通过 HER2 和 HER3 的激活介导的，导致 AKT 磷酸化升高。使用拉帕替尼抑制 HER 激活消除了 BTG2 敲低的影响，包括体外观察到的细胞迁移增加以及体内肿瘤发生和转移的增强。这些结果将 BTG2 依赖性效应与肿瘤进展联系起来，并提出了靶向抑制该通路可能与乳腺癌治疗相关的可能性。