Peroxiredoxin 1 interacts with androgen receptor and enhances its transactivation

Cancer Res. 2007 Oct 1;67(19):9294-303. doi: 10.1158/0008-5472.CAN-07-0651.


Although hypoxia is accepted as an important microenvironmental factor influencing tumor progression and treatment response, it is usually regarded as a static global phenomenon. Consequently, less attention is given to the impact of dynamic changes in tumor oxygenation in regulating the behavior of cancer cells. Androgen receptor (AR) signaling plays a critical role in prostate cancer. We previously reported that hypoxia/reoxygenation, an in vitro condition used to mimic an unstable oxygenation climate in a tumor, stimulates AR activation. In the present study, we showed that peroxiredoxin 1 (Prx1), a member of the peroxiredoxin protein family, acts as a key mediator in this process. We found that the aggressive LN3, C4-2, and C4-2B prostate cancer cell lines derived from LNCaP possess constitutively elevated Prx1 compared with parental cells, and display greater AR activation in response to hypoxia/reoxygenation. Although the cell survival-enhancing property of Prx1 has traditionally been attributed to its antioxidant activity, the reactive oxygen species-scavenging activity of Prx1 was not essential for AR stimulation because Prx1 itself was oxidized and inactivated by hypoxia/reoxygenation. Increased AR transactivation was observed when wild-type Prx1 or mutant Prx1 (C52S) lacking antioxidant activity was introduced into LNCaP cells. Reciprocal immunoprecipitation, chromatin immunoprecipitation, and in vitro pull-down assays corroborated that Prx1 interacts with AR and enhances its transactivation. We also show that Prx1 is capable of sensitizing a ligand-stimulated AR. Based on the above information, we suggest that disrupting the interaction between Prx1 and AR may serve as a fruitful new target in the management of prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Hypoxia
  • Cell Line, Tumor
  • Humans
  • Male
  • Oxygen / metabolism
  • Peroxidases / biosynthesis
  • Peroxidases / genetics
  • Peroxidases / metabolism*
  • Peroxiredoxins
  • Promoter Regions, Genetic
  • Prostate-Specific Antigen / genetics
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Signal Transduction
  • Transcriptional Activation
  • Transfection


  • Receptors, Androgen
  • Peroxidases
  • PRDX1 protein, human
  • Peroxiredoxins
  • Prostate-Specific Antigen
  • Oxygen