Glucose Concentration in Cell Culture Medium Influences the BRCA1-Mediated Regulation of the Lipogenic Action of IGF-I in Breast Cancer Cells

Moses O Koobotse, Dayane Schmidt, Jeff M. P. Holly, Claire M Perks*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Hyperglycaemia is a common metabolic alteration associated with breast cancer risk and progression. We have previously reported that BRCA1 restrains metabolic activity and proliferative response to IGF-I anabolic actions in breast cancer cells cultured in high glucose. Here, we evaluated the impact of normal glucose on these tumour suppressive roles of BRCA1. Human breast cancer cells cultured in normal and high glucose were treated with IGF-I (0-500ng/ml). Cellular responses were evaluated using immunoblotting, co-immunoprecipitation and cell viability assay. As we previously reported, IGF-I induced ACCA dephosphorylation by reducing the association between BRCA1 and phosphorylated ACCA in high glucose, and upregulated FASN abundance downstream of ACCA. However, these effects were not observed in normal glucose. Normal glucose conditions completely blocked IGF-I-induced ACCA dephosphorylation and FASN upregulation. Co-immunoprecipitation studies showed that normal glucose blocked ACCA dephosphorylation by increasing the association between BRCA1 and phosphorylated ACCA. Compared to high glucose, the proliferative response of breast cancer cells to IGF-I was reduced in normal glucose, whereas no difference was observed in normal mammary epithelial cells. Considering these results collectively, we conclude that normal glucose promotes the novel function of BRCA1 as a metabolic restraint of IGF-I actions. These data suggest that maintaining normal glucose levels may improve BRCA1 function in breast cancer and slow down cancer progression.
Original languageEnglish
Article number8674
Number of pages18
JournalInternational Journal of Molecular Sciences
Volume21
Issue number22
DOIs
Publication statusPublished - 17 Nov 2020

Keywords

  • Hyperglycaemia
  • BRCA1
  • IGF-I
  • fatty acid synthesis
  • breast cancer
  • ICEP

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