title: Active estrogen synthesis and its function in prostate cancer-derived stromal cells.
abstract: BACKGROUND
  It remains unclear whether estrogen is produced in prostate cancer (PCa) and how it functions in PCa.
  
  
  METHODS
  To examine the production of estrogen in PCa cells, the concentration of estrogen in the medium in which LNCaP cells and PCa-derived stromal cells (PCaSC) were co-cultured, was measured by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), while aromatase (CYP19) mRNA expression was confirmed by real-time polymerase chain reaction (RT-PCR) methods. To verify whether estrogen is synthesized from testosterone in PCaSC functions, PCaSC were co-cultured with breast cancer MCF-7-E10 cells, which were stably-transfected with ERE-GFP, in the presence of testosterone. GFP expression was detected when PCaSCs could synthesize estrogen. The proliferation of PC-3 cells in the presence of PCaSC was determined by cell count.
  
  
  RESULTS
  PCaSC metabolized excessive testosterone to estrogen, which activated estrogen receptor in breast cancer cells. Moreover, estrogen synthesized from testosterone in PCaSC regulated the proliferation of PC-3 cell via repression of some unknown growth factors that were secreted from PCaSC.
  
  
  CONCLUSIONS
  A chimeric co-culture method between breast cancer cells and PCaSC revealed the production of active estrogen in PCaSC. High-dose testosterone therapy might introduce a new potential strategy to treat CRPC.
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Ishikawa, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Machioka
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Ishikawa, Japan mizokami@med.kanazawa-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizokami
authors.affiliation: Division of Breast Surgery, Saitama Cancer Center, Saitama, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Ishikawa, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Izumi
authors.affiliation: Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Ishikawa, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D004967:Estrogens / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D011467:Prostate / Q000473:pathology*; D064129:Prostatic Neoplasms, Castration-Resistant; D011960:Receptors, Estrogen / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D013739:Testosterone
keywords: Castration-resistant prostate cancer; chimeric coculture; estrogen; prostate cancer-derived stromal cell; testosterone