Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Int J Mol Sci. 2023 Jun 16;24(12):10209. doi: 10.3390/ijms241210209.
The Insulin-like Growth Factor (IGF) system in breast cancer progression has been a matter of interest for decades, but targeting this system did not result in a successful clinical strategy. The system's complexity and homology of its two receptors-insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF-1R)-are possible causes. The IGF system maintains cell proliferation and also regulates metabolism, making it a pathway to explore. To understand the metabolic phenotype of breast cancer cells, we quantified their real-time ATP production rate upon acute stimulation with ligands-insulin-like growth factor 1 (1GF-1) and insulin. MCF-7L cells express both IGF-1R and IR, while tamoxifen-resistant MCF-7L (MCF-7L TamR) cells have downregulated IGF-1R with unchanged IR levels. Treating MCF-7L cells with 5 nM IGF-1 increased the glycolytic ATP production rate, while 10 nM insulin did not affect metabolism when compared with the control. Neither treatment altered ATP production in MCF-7L TamR cells. This study provides evidence of the relationship between metabolic dysfunction, cancer, and the IGF axis. In these cells, IGF-1R, and not IR, regulates ATP production.
胰岛素样生长因子（IGF）系统在乳腺癌进展中的作用已经引起了数十年的关注，但针对该系统的治疗并未产生成功的临床策略。这可能是由于该系统的复杂性及其两个受体（胰岛素受体[IR]和 1 型胰岛素样生长因子受体[IGF-1R]）的同源性所致。IGF 系统维持细胞增殖，还调节代谢，因此是一个值得探索的途径。为了了解乳腺癌细胞的代谢表型，我们定量检测了它们在急性受到配体（胰岛素样生长因子 1 [IGF-1]和胰岛素）刺激时实时的 ATP 产生速率。MCF-7L 细胞表达 IGF-1R 和 IR，而他莫昔芬耐药 MCF-7L（MCF-7L TamR）细胞下调了 IGF-1R，但 IR 水平不变。与对照组相比，用 5 nM IGF-1 处理 MCF-7L 细胞会增加糖酵解 ATP 的产生速率，而 10 nM 胰岛素则不会影响代谢。两种处理均未改变 MCF-7L TamR 细胞中的 ATP 产生。本研究为代谢功能障碍、癌症和 IGF 轴之间的关系提供了证据。在这些细胞中，是 IGF-1R 而不是 IR 调节 ATP 的产生。
