Co-expression of the androgen receptor and the transcription factor ZNF652 is related to prostate cancer outcome

Abstract

Abstract. 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 5·-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 organdefined 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.

A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone–Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation

“…In breast cancer cell lines ZBTB10 is suppressed by ROS-microRNA27a thereby enhancing ERα alpha expression and mediating estrogen effects [17]. The ZNF652 (17q21.32) locus codes for a DNA binding protein thought to act as a tumor suppressor gene in breast cancer [69], [70], [71] that is also co-expressed with the androgen receptor in prostate cancer [72]. TDGF3 , teratocarcinoma derived growth factor 3, is the only significant region identified on the X chromosome ((Xq22.3).…”

Prostate cancer in men of African origin

“…This newly identified SNP is located on an intron in a gene encoding a zinc-finger transcription factor (ZNF652) that interacts with a transcriptional repressor (CBFA2T3) 57 . ZNF652 has, in turn, been associated with decreased relapse-free survival when co-expressed with the AR in prostate tumours 58 . The 8q24 region, on the other hand, has been the subject of much scrutiny for the well-known MYC proto-oncogene 59 .…”

Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array

“…rs7210100 in intron 1 of ZNF652 has previously been identified as a prostate cancer susceptibility gene in African-American men 22 ; however, this variant is rare among individuals of European ancestry, and the correlation between rs11650494 and rs7210100 is modest in the YRI (Yoruba from Ibadan, Nigeria) population ( r 2 = 0.22), suggesting that rs11650494 represents an independent or European-specific prostate cancer risk association. In addition, ZNF652 has been reported to be highly expressed in the majority of prostate tumors and is associated with higher risk of relapse 23 .…”