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.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T27 T28 T29 T2 T30 T31 T32 T33 T3 T4 T5 T6 T7 T8 T9
CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL GENE-N GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-N CHEMICAL GENE-Y GENE-Y GENE-Y GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD TCDD Androgen 2,3,7,8-tetrachlorodibenzo-p-dioxin aryl hydrocarbon receptor AhR androgen receptor AR AR TCDD CAG repeat ARs CAG repeats AhR CYP1A1 AR CAG AR AR CAG TCDD AR AR Androgen receptor CAG repeat aryl hydrocarbon androgen TCDD 5α-dihydrotestosterone TCDD TCDD TCDD