A Mimic of the Tumor Microenvironment on GPR30 Gene Expression in Breast Cancer

Introduction: The G-protein coupled receptor 30 (GPR30) gene is a member of the G-protein coupled receptor (GPCR) family; involved in breast, endometrial, and ovarian cancers. Many GPCR receptors that are implicated in several types of human cancers are correlated with increased cell proliferation and tumor progression; especially GPR30 gene. Methods: The breast cancer MCF-7 and MDA-MB-231 cells were cultured with different concentrations of glucose (5.5, 11, and 25 mM) under normoxia/hypoxia for 24, 48, and 72 hours. Hypoxia conditions were created with Cobalt (II) chloride at a concentration of 100 μM in culture media. The scratch assay techniques were carried out to investigate the migration and finally, gene expression levels of GPR30 mRNA were investigated by quantitative Real-Time polymerase chain reaction. Results: The MDA-MB-231 cells adaptation in hypoxic conditions is evident which enables cell survival, whereas it results in cell proliferation in the MCF-7 cells. The increased expression of GPR30 (P≤0.0001) was found to be associated with the promoted metastasis in the MDA-MB-231 cells, while an inverse relationship was seen between the GPR30 mRNA level and cellular migration in the MCF-7 cells. We found that hypoxia induces the expression of GPR30 in MDA-MB-231 cells, and MCF-7 cells; exposed to hypoxia, had a heterogeneous expression. Conclusions: Increases /decreases in glucose concentration and hypoxia lead to changes in the expression profiles of cancer cells. The upregulation of GPR30 expression was associated with a higher risk of breast cancer metastasis; demonstrating its importance as an applicant bio-target for cancer therapy.