Type II diabetes is characterized by hyperglycemia, or increased glucose serum concentrations, which in turn has been correlated as a risk factor for the development of breast cancer through interactions with the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Other studies have suggested that breast carcinoma and invasive ductal carcinoma have a significant increase in 2 insulin independent glucose transporters, which has been linked to their more malignant and metastatic phenotypes. Therefore, we hypothesized that the build-up of 3' phosphatidylinositol products from cancer related PI3K over activity may serve as a key regulator, and possibly biomarker, for specific types of breast cancers. In order to further explore the relationship between hyperglycemia and breast cancer initiation, breast tissue cell lines (normal, MCF10A; EGFR+, MCF7; HER2+, SKBR3; and metastatic triple negative (ER-, PR-, HER2-), MDA-MB-468) were incubated for 24 hours in normal to hyperglycemic serum concentrations (5.5, 10, 25, and 50 mM glucose). We then measured the relative abundancies of the 3’ phosphorylated phosphatidylinositol (PI) species—mono-phosphorylated PI3P, di-phosphorylated PI(3,4)P2, and tri-phosphorylated PIP3—in each cell line through confocal fluorescence microscopy analysis. MCF10As supported our hypothesis with an increase in PI(3,4)P2 and PIP3 concentration with increasing serum glucose concentration. However, we see variations in the results of the MCF7s where PI3,4P2 accumulation is the key indicator, suggesting a linked to the reported upregulation of PI3K activity and SHIP2 (5’-phosphatase) expression, and downregulation of PTEN (3’-phosphatase). Furthermore, that observation was supported by the SKBR3s, which has a reported upregulation of PI3K activity and downregulation of PTEN expression, whose PIP3 results reflected the MCF7s without SHIP2 effects. We expect that MDA-MB-468 cells, which have a reported increased PI3K activity and decreased PTEN expression, will respond similarly to MCF7s but will have a significant PIP2 and PIP3 build-up. We suggest that the results of our study will provide insight to the potential of using lipidomics to distinguish between various types of breast cancer and their related metastatic behavior.

Using lipidomics to identify biomarkers for hyperglycemic onset breast cancer

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.