title: Transcript Levels of Androgen Receptor Variant 7 and Ubiquitin-Conjugating Enzyme 2C in Hormone Sensitive Prostate Cancer and Castration-Resistant Prostate Cancer.
abstract: This study is designed to identify the androgen receptor variant 7 (AR-V7) status, clinical significance of AR-V7 in hormone sensitive prostate cancer (HSPC). Then, we evaluated AR-V7 and changes of its target gene, ubiquitin-conjugating enzyme E2C (UBE2C) which is an anaphase-promoting complex/cyclosome (APC/C)-specific ubiquitin-conjugating enzyme, in castration-resistant prostate cancer (CRPC) in serial tumor biopsies from patients receiving androgen deprivation therapy.
  
  
  
  We used RT-PCR and Q-PCR assay to evaluate AR-V7, androgen receptor full length (AR-FL), and UBE2C in tumor biopsies from patients with HSPC and CRPC. We examined associations between mRNA expression of AR-V7 and clinicopathologic factors. Furthermore, to identify other potential genes involved in the development of CRPC, RNA sequencing was conducted, using paired prostate cancer (PCa) tissues obtained immediately prior to treatment and at the time of therapeutic resistance.
  
  
  
  A total of 13 HSPC patients and three CRPC patients were enrolled. Neither a high Gleason score (score of 8 and 9) nor a high risk of PCa (a high risk of locally advanced PCa according to NCCN guidelines) was correlated with mRNA expression of AR-V7 in HSPC (P = 0.153 and P = 0.215). The mRNA expression of AR-FL, but not AR-V7, was significantly associated with the mRNA expression of UBE2C level in HSPC (P = 0.007). However, increased expression of AR-V7, not AR-FL, paralleled increased expression of UBE2C in the CRPC specimens (P = 0.03). AR-V7 expression status before ADT was likely related to shorter CRPC development in patients treating ADT. The result of the RNA-sequencing analysis using serial samples from the same patient before and after castration demonstrated an increased level of the PI3K regulatory subunit 1 (P = 0.018).
  
  
  
  Our study revealed the role of UBE2C as a marker of the androgen signaling pathway in PCa. Differential gene expression analysis using serial samples from the same patient before and after castration revealed potential genes and pathways involved in development of CRPC. Further studies are needed to determine whether these genes and pathways are potential therapeutic target for CRPC. Prostate 77:60-71, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea.
authors.forename: Chan Ho
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea.
authors.forename: Ja Yoon
authors.initials: JY
authors.lastname: Ku
authors.affiliation: Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ha
authors.affiliation: Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
authors.affiliation: Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea.
authors.forename: Jeong Zoo
authors.initials: JZ
authors.lastname: Lee
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Choung-Soo
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea.|Biomedical Research Institute, Pusan National University School of Medicine, Busan, Republic of Korea.
authors.forename: Hong Koo
authors.initials: HK
authors.lastname: Ha
mesh_terms: D000368:Aged; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000378:metabolism*; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D014158:Transcription, Genetic / Q000502:physiology*; D044763:Ubiquitin-Conjugating Enzymes / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; C105156:UBE2C protein, human; D044763:Ubiquitin-Conjugating Enzymes
keywords: UBE2C; androgen receptor; castration-resistant prostate cancer