Androgen and anti-androgen treatment modulates androgen receptor activity and DJ-1 stability.
BACKGROUND
Mechanisms regulating the transition from hormone responsive to hormone refractory prostate cancer (PCa) have remained unclear.


METHODS
We analyzed androgen and anti-androgen treatment on endogenous AR activity in primary human prostate epithelial (HPE) cells cultured directly from patient radical prostatectomy specimens utilizing a transiently infected gene reporter (TIGR) assay.


RESULTS
Flutamide treatment exhibited agonist activities in HPE cells derived from tumor and non-tumor specimens which contained wild-type AR. After proteomic comparison of these cells to those where flutamide functioned normally as an antagonist, we identified DJ-1, a positive regulator of AR. DJ-1 expression increased in HPE and LNCaP cells during flutamide treatment as a result of DJ-1 protein stabilization.


CONCLUSIONS
Stabilization of AR and its co-regulators in the absence of androgen may partially account for anti-androgen withdrawal syndrome and potentially contribute to the development of hormone refractory PCa.
Pitkänen-Arsiola
Tiina
T
Institute of Applied Biotechnology, University of Kuopio, Kuopio, Finland.
Tillman
J Erin
JE
Gu
Guangyu
G
Yuan
Jialing
J
Roberts
Richard L
RL
Wantroba
Marcus
M
Coetzee
Gerhard A
GA
Cookson
Michael S
MS
Kasper
Susan
S
D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D004355:Drug Stability; D015180:Electrophoresis, Gel, Two-Dimensional; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D005485:Flutamide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D008297:Male; D008854:Microscopy, Electron; D015513:Oncogene Proteins / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D011467:Prostate / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics; D000071617:Protein Deglycase DJ-1; D011944:Receptors, Androgen / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D000728:Androgens; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D011944:Receptors, Androgen; D005485:Flutamide; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1