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

Björk, Christel LU and Giwercman, Yvonne LU (2012) In Reproductive Toxicology
Abstract
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... (More)
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. (Less)
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organization
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Contribution to journal
publication status
published
subject
in
Reproductive Toxicology
publisher
Elsevier
external identifiers
  • WOS:000314003900018
  • PMID:23117151
  • Scopus:84871920038
ISSN
1873-1708
DOI
10.1016/j.reprotox.2012.10.010
language
English
LU publication?
yes
id
377cfec0-72f5-4b39-ab7b-ee2a48dc59b5 (old id 3219306)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23117151?dopt=Abstract
date added to LUP
2012-12-03 11:22:46
date last changed
2016-12-04 04:38:18
@misc{377cfec0-72f5-4b39-ab7b-ee2a48dc59b5,
  abstract     = {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.},
  author       = {Björk, Christel and Giwercman, Yvonne},
  issn         = {1873-1708},
  language     = {eng},
  month        = {10},
  publisher    = {ARRAY(0xa065518)},
  series       = {Reproductive Toxicology},
  title        = {Androgen receptor CAG repeat length modifies the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on receptor activity in human prostate cells.},
  url          = {http://dx.doi.org/10.1016/j.reprotox.2012.10.010},
  year         = {2012},
}