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Article

Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer

1
Department of Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3
Department of Chemistry, Indiana University Bloomington, IN 47405, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2320; https://doi.org/10.3390/ijms21072320
Received: 22 February 2020 / Revised: 23 March 2020 / Accepted: 25 March 2020 / Published: 27 March 2020
(This article belongs to the Special Issue Phosphoinositides and Downstream Signalling Molecules)
Studies have suggested that type 2 diabetes (T2D) is associated with a higher incidence of breast cancer and related mortality rates. T2D postmenopausal women have an ~20% increased chance of developing breast cancer, and women with T2D and breast cancer have a 50% increase in mortality compared to breast cancer patients without diabetes. This correlation has been attributed to the general activation of insulin receptor signaling, glucose metabolism, phosphatidylinositol (PI) kinases, and growth pathways. Furthermore, the presence of breast cancer specific PI kinase and/or phosphatase mutations enhance metastatic breast cancer phenotypes. We hypothesized that each of the breast cancer subtypes may have characteristic PI phosphorylation profiles that are changed in T2D conditions. Therefore, we sought to characterize the PI phosphorylation when equilibrated in normal glycemic versus hyperglycemic serum conditions. Our results suggest that hyperglycemia leads to: 1) A reduction in PI3P and PIP3, with increased PI4P that is later converted to PI(3,4)P2 at the cell surface in hormone receptor positive breast cancer; 2) a reduction in PI3P and PI4P with increased PIP3 surface expression in human epidermal growth factor receptor 2-positive (HER2+) breast cancer; and 3) an increase in di- and tri-phosphorylated PIs due to turnover of PI3P in triple negative breast cancer. This study begins to describe some of the crucial changes in PIs that play a role in T2D related breast cancer incidence and metastasis. View Full-Text
Keywords: hyperglycemia; hormone receptor positive breast cancer; HER2 positive breast cancer; triple negative breast cancer; PI3K/AKT signaling hyperglycemia; hormone receptor positive breast cancer; HER2 positive breast cancer; triple negative breast cancer; PI3K/AKT signaling
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MDPI and ACS Style

Devanathan, N.; Jones, S.; Kaur, G.; Kimble-Hill, A.C. Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer. Int. J. Mol. Sci. 2020, 21, 2320. https://doi.org/10.3390/ijms21072320

AMA Style

Devanathan N, Jones S, Kaur G, Kimble-Hill AC. Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer. International Journal of Molecular Sciences. 2020; 21(7):2320. https://doi.org/10.3390/ijms21072320

Chicago/Turabian Style

Devanathan, Nirupama, Sandra Jones, Gursimran Kaur, and Ann C. Kimble-Hill 2020. "Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer" International Journal of Molecular Sciences 21, no. 7: 2320. https://doi.org/10.3390/ijms21072320

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