Hyperglycemia promotes an aggressive phenotype in breast cancer cells

ABSTRACT: Diabetes and breast cancer are common diseases with a major impact on the health sector in Mexico and worldwide. Epidemiological and experimental works support the link between type 2 diabetes and breast cancer; these data support that insulin resistance, hyperglycemia, hyperinsulinemia, and elevated levels of IGF-1 in patients with type II diabetes mellitus promote growth and invasiveness of tumor cells. The aim of the present work was to determine, by microarray, the mechanisms of action and signaling of a hyperglycemic microenvironment in the cell line (MDA-MB-231) and its effect to treatment with cisplatin (CCP). MDA-MB-231 breast cancer cells were cultured in DMEM medium, supplemented with 10% fetal bovine serum and antibiotics at 5% CO2, at 37 ˚C. We proceeded to extract total RNA for the analysis of microarrays under LG (low glucose) and HG (high glucose) conditions; for the cDNA synthesis, it was labeled with dUTP-Cy3 or dUTP-Cy5 fluorophores, using a CyScribe Firs-Strand cDNA kit. The analysis was carried out through the KEGG pathways program; some bioenergetic metabolism processes (glycolysis, biosynthesis of purines and pyrimidines, and metabolism of glycerol phospholipids) were found altered, which fulfill the feedback function to the cellular microenvironment, activating some signaling processes, such as the Hippo route, PI3K-Akt, Jak-STAT, MAPK, Ras, Wnt/β-catenin, apoptosis, and favoring an aggressive phenotype and drug resistance in a hyperglycemic microenvironment. The microarray analysis was validated by qRT-PCr of the tetraspanin and Frizzled genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE136277 | GEO | 2019/08/24

REPOSITORIES: GEO