Estrogen Simulation of Glucose Transporter Expression in Endometrial Cancer Cells

Type I endometrial cancer responds to estrogen and is highly associated with obesity. Estrogen levels are elevated in obese women, perhaps indicating a link between estrogen and obesity-associated endometrial cancer. Previous studies have shown that estrogen regulates expression and activity of proteins involved in glucose metabolism, including glucose transporters. Additionally, expression of the glucose transporter, GLUT6 was elevated in malignant endometrium of obese women compared to non-tumor tissue. Loss of GLUT6 expression in endometrial cancer cells resulted in cell death, indicating a potential role of GLUT6 in tumor growth. Importantly, the GLUT6 promoter contains estrogen response elements. Therefore, we evaluated whether estrogen regulates GLUT6 expression. Human endometrial cancer cells (MFE296) were stimulated with estrogen, and expression of GLUT1, which responds to estrogen and served as the positive control, and GLUT6, were examined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). As expected, GLUT1 expression increased with estrogen stimulation; however, there was no significant change in expression of GLUT6. These results indicate that GLUT6 expression does not parallel GLUT1 in response to estrogen in MFE296 cells. Future studies will be designed to test different concentrations of estrogen in additional endometrial cancer cell lines and to examine the effect of estrogen on GLUT6 protein to identify potential conditions of estrogen-dependent regulation.