title: Intracrine androgen biosynthesis in renal cell carcinoma.
abstract: BACKGROUND
  Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression.
  
  
  METHODS
  Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume.
  
  
  RESULTS
  We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01).
  
  
  CONCLUSIONS
  Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.
authors.affiliation: Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Geun Taek
authors.initials: GT
authors.lastname: Lee
authors.affiliation: Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.|Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Han
authors.affiliation: Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.|Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Kwon
authors.affiliation: Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Rutveej
authors.initials: R
authors.lastname: Patel
authors.affiliation: Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Parth K
authors.initials: PK
authors.lastname: Modi
authors.affiliation: Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Seok Joo
authors.initials: SJ
authors.lastname: Kwon
authors.affiliation: Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Izak
authors.initials: I
authors.lastname: Faiena
authors.affiliation: Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Patel
authors.affiliation: Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.|Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Singer
authors.affiliation: Department of Urology, Asan Medical Center, Seoul 05505, Korea.
authors.forename: Han-Jong
authors.initials: HJ
authors.lastname: Ahn
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.|Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors.forename: Isaac Y
authors.initials: IY
authors.lastname: Kim
mesh_terms: D000069501:Abiraterone Acetate / Q000494:pharmacology; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009570:Nitriles; D009919:Orchiectomy; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000494:pharmacology; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C410798:AR protein, human; D000728:Androgens; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D010669:Phenylthiohydantoin; D013739:Testosterone; C540278:enzalutamide; D000069501:Abiraterone Acetate