DJ-1 binds androgen receptor directly and mediates its activity in hormonally treated prostate cancer cells.
The oncogene DJ-1 has been associated with multiple cancers, including prostate cancer, where it can be stabilized by androgens and antiandrogens. However, little data exist on the expression pattern and function of DJ-1 in prostate cancer. To address the function of DJ-1 in prostate, a yeast two-hybrid screen was done to identify novel DJ-1 binding proteins. The androgen receptor (AR) was identified and confirmed as a DJ-1 binding partner. This is the first evidence that DJ-1 directly interacts with AR. We also show that modulation of DJ-1 expression regulated AR transcriptional activity. Importantly, both the subcellular localization of DJ-1 and the interaction with AR are regulated by androgens and antiandrogens. Additionally, immunohistochemical staining on two human prostate cancer tissue arrays was done providing the first large-scale expression analysis of DJ-1 in prostate. DJ-1 expression did not change with Gleason pattern but increased after androgen deprivation therapy, indicating that it may be involved in the development of androgen independence. These data provide a novel mechanism where DJ-1-mediated regulation of AR may promote the progression of prostate cancer to androgen independence.
Tillman
J Erin
JE
Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-2765, USA.
Yuan
Jialing
J
Gu
Guangyu
G
Fazli
Ladan
L
Ghosh
Ritwik
R
Flynt
Alex S
AS
Gleave
Martin
M
Rennie
Paul S
PS
Kasper
Susan
S
D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000172:deficiency; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D014158:Transcription, Genetic
D000726:Androgen Antagonists; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D011944:Receptors, Androgen; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1