Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer
| Autor: | Sandra Jones, Nirupama Devanathan, Ann C. Kimble-Hill, Gursimran Kaur |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Receptor
ErbB-2 Breast Neoplasms Type 2 diabetes Phosphatidylinositols HER2 positive breast cancer Catalysis Article Metastasis Inorganic Chemistry lcsh:Chemistry Breast cancer Cell Line Tumor medicine Phosphatidylinositol phosphorylation Biomarkers Tumor Humans Breast Physical and Theoretical Chemistry Phosphorylation skin and connective tissue diseases Molecular Biology lcsh:QH301-705.5 Spectroscopy Triple-negative breast cancer biology Kinase business.industry Organic Chemistry General Medicine medicine.disease Metastatic breast cancer Receptor Insulin Computer Science Applications Insulin receptor Phosphotransferases (Alcohol Group Acceptor) Glucose Diabetes Mellitus Type 2 lcsh:Biology (General) lcsh:QD1-999 triple negative breast cancer biology.protein Cancer research MCF-7 Cells Female hyperglycemia business PI3K/AKT signaling hormone receptor positive breast cancer Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 7 International Journal of Molecular Sciences, Vol 21, Iss 2320, p 2320 (2020) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21072320 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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