Abstract
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.
Keywords:
breast cancer; insulin; insulin receptor; metabolic dysregulation; type 1 insulin-like growth factor; type 1 insulin-like growth factor receptor.