Androgen receptor CAG repeat length modifies the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on receptor activity in human prostate cells

Increased incidence of prostate cancer has been reported in men exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD acts through the aryl hydrocarbon receptor (AhR), which interacts with the androgen receptor (AR). The AR gene contains a polymorphic CAG repeat that influences its transcriptional activity. We investigated the influence of TCDD on prostate cancer cells (PC-3) and non-tumor prostate cells (PNT1A) on 5α-dihydrotestosterone-activated ARs containing CAG repeats within normal length range (16, 22, and 28). The AhR target gene CYP1A1 mRNA expression was induced by TCDD, but was not affected by the AR CAG length. TCDD had no effect on AR activity in PC-3 cells, whereas the shortest AR variant was induced by TCDD in PNT1A cells. In conclusion, the CAG length dependent effect of TCDD on AR activity in PNT1A, but not in PC-3 cells, indicates as a cell-specific effect of TCDD on AR activity.

► TCDD had no impact on androgen receptor activity in prostate cancer cells.
► In non-malignant cells, the effect was dependent on the androgen receptor variant.
► No effect of TCDD was found in the absence of androgen.