Endocrine Abstracts

Cancer cells show different metabolic requirements than normal cells, being the high rate of glucose uptake one of the most important aspects. An increase in glucose uptake has been associated mainly with GLUT1 overexpression but may also involve other transporters including GLUT4, whose presence in prostate cancer cells was recently discovered in our laboratory. Moreover, androgens stimulate anabolic synthesis and increase glucose uptake. Despite this, the regulation of GLUT transporters by androgens has been scarcely studied. Thus, the aim of this work was to study the relation between GLUT1/4 and the androgen receptor (AR) signalling pathway in prostate cancer cells. GLUT1/4 and AR protein levels were analysed by immunoblot. Glucose uptake and glucose concentration in culture media were measured using 2-deoxyglucose and a glucometer respectively. The analysis of cell cycle was performed by flow cytometry. Finally, cell viability and proliferation were estimated by MTT reduction and Hoechst staining. Results show that GLUT1/4 expression is dependent of glucose concentration in culture media. GLUT1 was overexpressed when glucose concentration was reduced in the androgen-sensitive LNCaP and PC-3AR cells, being the number of cells in G1 phase lower. Glucose consumption was also higher in PC-3AR cells than in androgen-insensitive PC-3 cells. On the other hand, the effect of insulin (that stimulates GLUT4 transport) or indinavir (that inhibits GLUT4) were higher in androgen-insensitive cells. Moreover, AR signalling was involved in GLUT expression. Nuclear translocation of AR was increased at low glucose concentration correlating with the increment of GLUT1 levels. In addition, DHT stimulated glucose uptake and GLUT1 levels while bicalutamide (an androgen inhibitor) prevented this increment in androgen-sensitive LNCaP cells. In conclusion, AR pathway favours GLUT1 expression and functioning, while might be related to its carcinogenic properties in the prostate while GLUT4 transporter is more involved in glucose uptake in androgen-insensitive prostate cancer cells.

Disclosure: This work was supported by Ministerio de Economía y Competitivad, Gobierno de España (MINECO-13-BFU2012-38779).