Endocrine Abstracts

Mycophenolate mofetil (MYC) is widely used in transplant medicine as an immunosuppressant drug to prevent rejection in organ transplantation. In this work we investigated the effect of MYC on the activity of androgen receptor (AR) by employing gene reporter assay (GRA) and PCR in prostate cancer cell line 22Rv1.

Slight but significant activation of AR was observed for cells treated with MYC in stably transfected 22Rv1 cells (AIZ-AR). Moreover, significant stimulation of dihydrotestosterone (DHT)-inducible AR-dependent luciferase activity by MYC was observed. AR-target gene KLK3 (prostate specific antigen, PSA) mRNA was induced dose-dependently and consistently with GRA. DHT-inducible KLK3 mRNA was increased by MYC as well. Since we found that MYC induced the expression of KLK3 and activated AR, we investigated whether MYC affects the proliferation of prostatic cells. However, we observed opposite effect of MYC on proliferation. Only two lowest concentrations of MYC had positive effect on cell proliferation, but for 24h only, not for 48 hrs.

In conclusion, we found that MYC is an activator of AR and induced KLK3 mRNA in the prostate cancer cell line 22Rv1. However, we did not find correlation between AR activation by MYC and cell proliferation. In any case, herein we provide important findings which bring new information about mechanism of action of mycophenolate mofetil on AR.