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Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer

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...

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Autores principales: Devanathan, Nirupama, Jones, Sandra, Kaur, Gursimran, Kimble-Hill, Ann C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177416/
https://www.ncbi.nlm.nih.gov/pubmed/32230859
http://dx.doi.org/10.3390/ijms21072320
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author Devanathan, Nirupama
Jones, Sandra
Kaur, Gursimran
Kimble-Hill, Ann C.
author_facet Devanathan, Nirupama
Jones, Sandra
Kaur, Gursimran
Kimble-Hill, Ann C.
author_sort Devanathan, Nirupama
collection PubMed
description 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.
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spelling pubmed-71774162020-04-28 Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer Devanathan, Nirupama Jones, Sandra Kaur, Gursimran Kimble-Hill, Ann C. Int J Mol Sci Article 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. MDPI 2020-03-27 /pmc/articles/PMC7177416/ /pubmed/32230859 http://dx.doi.org/10.3390/ijms21072320 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Devanathan, Nirupama
Jones, Sandra
Kaur, Gursimran
Kimble-Hill, Ann C.
Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer
title Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer
title_full Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer
title_fullStr Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer
title_full_unstemmed Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer
title_short Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer
title_sort using phosphatidylinositol phosphorylation as markers for hyperglycemic related breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177416/
https://www.ncbi.nlm.nih.gov/pubmed/32230859
http://dx.doi.org/10.3390/ijms21072320
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