Glucose Concentration in Cell Culture Medium Influences the BRCA1-Mediated Regulation of the Lipogenic Action of IGF-I in Breast Cancer Cells
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...
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doaj-a9761c7d808246bda657c891a18ee6022020-11-25T03:59:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-01218674867410.3390/ijms21228674Glucose Concentration in Cell Culture Medium Influences the BRCA1-Mediated Regulation of the Lipogenic Action of IGF-I in Breast Cancer CellsMoses O. Koobotse0Dayane Schmidt1Jeff M. P. Holly2Claire M. Perks3IGFs & Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol BS10 5NB, UKIGFs & Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol BS10 5NB, UKIGFs & Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol BS10 5NB, UKIGFs & Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol BS10 5NB, UKHyperglycaemia 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 physiological glucose on these tumour suppressive roles of BRCA1. Human breast cancer cells cultured in normal physiological and high glucose were treated with IGF-I (0–500 ng/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 physiological glucose conditions completely blocked IGF-I-induced ACCA dephosphorylation and FASN upregulation. Co-immunoprecipitation studies showed that normal physiological 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 physiological 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.https://www.mdpi.com/1422-0067/21/22/8674hyperglycaemiaBRCA1IGF-Ifatty acid synthesisbreast cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Moses O. Koobotse Dayane Schmidt Jeff M. P. Holly Claire M. Perks |
spellingShingle |
Moses O. Koobotse Dayane Schmidt Jeff M. P. Holly Claire M. Perks Glucose Concentration in Cell Culture Medium Influences the BRCA1-Mediated Regulation of the Lipogenic Action of IGF-I in Breast Cancer Cells International Journal of Molecular Sciences hyperglycaemia BRCA1 IGF-I fatty acid synthesis breast cancer |
author_facet |
Moses O. Koobotse Dayane Schmidt Jeff M. P. Holly Claire M. Perks |
author_sort |
Moses O. Koobotse |
title |
Glucose Concentration in Cell Culture Medium Influences the BRCA1-Mediated Regulation of the Lipogenic Action of IGF-I in Breast Cancer Cells |
title_short |
Glucose Concentration in Cell Culture Medium Influences the BRCA1-Mediated Regulation of the Lipogenic Action of IGF-I in Breast Cancer Cells |
title_full |
Glucose Concentration in Cell Culture Medium Influences the BRCA1-Mediated Regulation of the Lipogenic Action of IGF-I in Breast Cancer Cells |
title_fullStr |
Glucose Concentration in Cell Culture Medium Influences the BRCA1-Mediated Regulation of the Lipogenic Action of IGF-I in Breast Cancer Cells |
title_full_unstemmed |
Glucose Concentration in Cell Culture Medium Influences the BRCA1-Mediated Regulation of the Lipogenic Action of IGF-I in Breast Cancer Cells |
title_sort |
glucose concentration in cell culture medium influences the brca1-mediated regulation of the lipogenic action of igf-i in breast cancer cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-11-01 |
description |
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 physiological glucose on these tumour suppressive roles of BRCA1. Human breast cancer cells cultured in normal physiological and high glucose were treated with IGF-I (0–500 ng/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 physiological glucose conditions completely blocked IGF-I-induced ACCA dephosphorylation and FASN upregulation. Co-immunoprecipitation studies showed that normal physiological 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 physiological 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. |
topic |
hyperglycaemia BRCA1 IGF-I fatty acid synthesis breast cancer |
url |
https://www.mdpi.com/1422-0067/21/22/8674 |
work_keys_str_mv |
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