Co-expression of the androgen receptor and the transcription factor ZNF652 is related to prostate cancer outcome.
ZNF652, a DNA binding transcription factor, was previously suggested to be differentially expressed in prostate cancer. This study investigated if the expressions of ZNF652 and androgen receptor (AR) in prostate cancer are associated with prostate specific antigen (PSA) defined relapse. ZNF652 and AR immunoreactivity were evaluated in prostate tissues from a cohort of 121 patients with prostate cancer and associations with disease outcome determined. To assess if ZNF652 can influence AR expression, or vice versa, levels of expression of ZNF652, AR and PSA were determined in the prostate cell line LNCaP following induction of AR activity by 5alpha-dihydrotestosterone, or knockdown of ZNF652 expression. Two thirds of prostate tumors retained high levels of ZNF652 (71/109 cases) and 50% of tumors high levels of AR (57/113). There was a significant decrease (p=0.005) in relapse-free survival of patients with high expression levels of both ZNF652 and AR and this was independent of preoperative PSA and seminal vesicle involvement. Modulation of either AR or ZNF652 expression levels in LNCaP cells was not associated with any corresponding changes to the levels of either ZNF652 or AR, respectively. High levels of expression of both AR and ZNF652 in clinically organ-defined prostate cancer are associated with a statistically increased risk of relapse. The ZNF652 and AR transcription factors are acting independently and it is proposed that the continued maintenance of expression of ZNF652 in AR positive cells results in a gene expression pattern that contributes to the relapse.
Callen
David F
DF
Breast Cancer Genetics Group, Discipline of Medicine, University of Adelaide, Adelaide 5000, SA, Australia. david.callen@adelaide.edu.au
Ricciardelli
Carmela
C
Butler
Miriam
M
Stapleton
Alan
A
Stahl
Jurgen
J
Kench
James G
JG
Horsfall
David J
DJ
Tilley
Wayne D
WD
Schulz
Renee
R
Nesland
Jahn M
JM
Neilsen
Paul M
PM
Kumar
Raman
R
Holm
Ruth
R
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011944:Receptors, Androgen; C525993:ZNF652 protein, human; D017430:Prostate-Specific Antigen