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胰岛素受体丧失会影响小鼠乳腺瘤发生

Lauren Podmore¹, Yekaterina Poloz², Catherine Iorio²

¹Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Research Tower, Toronto, ON M5G 1L7, Canada.

|November 1, 2023

概括

肥胖加重了乳腺癌 (BC) 的结果. 研究人员发现,在小鼠模型中删除胰岛素受体 (INSR) 延迟了BC发作,这表明INSR对瘤发作至关重要.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
内分泌学在内分泌学.

背景情况:

肥胖和相关的高胰岛素血症会对乳腺癌 (BC) 的预后和存活率产生负面影响.
胰岛素受体 (INSR) 在高达80%的BC中过度表达,与不良结果相关.
超胰岛素血症在肥胖中很普遍,与增加BC死亡率和复发风险有关.

研究的目的:

研究胰岛素受体 (INSR) 在乳腺瘤发生中的作用.
为了确定INSR删除是否会影响小鼠模型中的瘤发病,进展或转移.

主要方法:

产生的MMTV驱动的多瘤中T (PyMT) 和ErbB2 / Her2 BC.的小鼠模型.
在这些模型中进行了乳腺上皮受限的胰岛素受体 (INSR) 删除.
进行了老鼠瘤和细胞的纵向表型表征.

主要成果:

在两种BC模型中,删除一个或两个INSR副本显著延迟了瘤发病和减少了瘤负担.
INSR 删除主要影响瘤开始,对进展或转移无显著影响.
在乳腺上皮细胞中,INSR保持了生物能量表型,独立于其酶活性.

结论:

胰岛素受体 (INSR) 在启动乳腺瘤发生过程中起着关键作用.
INSR对瘤发生的影响似乎是剂量依赖的,观察到值效应.
准INSR可能提供预防乳腺癌发病的治疗策略.

关键词:

CP: 癌症癌症癌症生物能量健身生物能量健身乳腺癌乳腺癌乳腺癌基因改造的小鼠模型胰岛素受体的胰岛素受体乳腺瘤的产生.

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