Active estrogen synthesis and its function in prostate cancer-derived stromal cells

Kazuaki Machioka, Atsushi Mizokami, Yuri Yamaguchi, Kouji Izumi, Shinichi Hayashi, Mikio Namiki

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Background: It remains unclear whether estrogen is produced in prostate cancer (PCa) and how it functions in PCa.

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.

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.

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 (LCMS/ 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 stablytransfected 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.

Original languageEnglish
Pages (from-to)221-228
Number of pages8
JournalAnticancer research
Volume35
Issue number1
Publication statusPublished - 2015 Jan 1

Keywords

  • Castration-resistant prostate cancer
  • Chimeric coculture
  • Estrogen
  • Prostate cancer-derived stromal cell
  • Testosterone

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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