乳腺癌细胞系对胰岛素的特异反应:对增殖和迁移的影响
Mattia Melloni1, Domenico Sergi1, Angelina Passaro1
1Department of Translational Medicine, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy.
International journal of molecular sciences
|August 14, 2025
概括
高胰岛素水平,而不是高葡萄糖,影响乳腺癌 (BC) 的进展. 超胰岛素血症促进了对激素敏感的BC细胞的增殖和三阴性细胞的迁移,这表明有针对性的胰岛素途径疗法.
科学领域:
- 内分泌学 在内分泌学.
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 糖尿病的微环境,标志着高血糖和高胰岛素,影响乳腺癌 (BC) 的进展.
- 将糖尿病微环境与BC进展联系起来的细胞机制需要进一步阐明.
研究的目的:
- 研究超生理葡萄糖和胰岛素水平对激素反应 (MCF-7) 和三阴性 (MDA-MB-231) BC细胞模型的影响.
- 分析高胰岛素血症对PI3K/AKT和MAPK通路,细胞增殖,细胞循环和不同BC亚型的迁移的影响.
主要方法:
- 暴露MCF-7和MDA-MB-231细胞在高葡萄糖和/或高胰岛素条件下.
- 对AKT和MAPK通路激活 (酸化) 的分析.
- 评估细胞增殖,细胞循环分布和细胞迁移.
主要成果:
- 高胰岛素激活了两个细胞系中的AKT通路.
- 超胰岛素血症仅在MCF-7细胞中刺激增殖和改变细胞周期分布.
- 高葡萄糖单独没有影响增殖;高胰岛素与高葡萄糖结合时没有进一步增加增殖.
- 在长期高胰岛素血症暴露后,MDA-MB-231细胞的迁移增加,但不增殖.
- 抑制AKT阻断了MCF-7细胞中的增殖刺激.
结论:
- 慢性高胰岛素血症,而不是高血糖,对乳腺癌产生亚型特异性影响.
- 超胰岛素血症通过AKT激活促进激素敏感BC细胞的增殖.
- 超胰岛素血症增强了三阴BC细胞的迁移.
- 准胰岛素通路可能为特定的乳腺癌亚型提供治疗潜力.
相关概念视频
01:28Insulin: The Receptor and Signaling Pathways
1.5K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.5K
01:22PI3K/mTOR/AKT Signaling Pathway
4.0K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
4.0K