TY - JOUR T1 - Active Estrogen Synthesis and its Function in Prostate Cancer-derived Stromal Cells JF - Anticancer Research JO - Anticancer Res SP - 221 LP - 227 VL - 35 IS - 1 AU - KAZUAKI MACHIOKA AU - ATSUSHI MIZOKAMI AU - YURI YAMAGUCHI AU - KOUJI IZUMI AU - SHINICHI HAYASHI AU - MIKIO NAMIKI Y1 - 2015/01/01 UR - http://ar.iiarjournals.org/content/35/1/221.abstract N2 - Background: It remains unclear whether estrogen is produced in prostate cancer (PCa) and how it functions in PCa. Materials and 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. Conclusion: 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. ER -