Androgen suppresses testicular cancer cell growth in vitro and in vivo

Hideo Nakagawa, Takashi Ueda, Saya Ito, Takumi Shiraishi, Hidefumi Taniguchi, Naruhiro Kayukawa, Hiroyuki Nakanishi, So Ushijima, Motohiro Kanazawa, Terukazu Nakamura, Yoshio Naya, Fumiya Hongo, Kazumi Kamoi, Koji Okihara, Osamu Ukimura

Research output: Contribution to journalArticlepeer-review

Abstract

Silencing of androgen receptor (AR)-meditated androgen signaling is thought to be associated with the development of testicular germ cell tumors (TGCTs). However, the role of the androgen/AR signal in TGCT development has not been investigated. In this study, we show that the androgen/AR signal suppressed the cell growth of seminomas (SEs), a type of TGCT, in vitro and in vivo. Growth of SE cells was suppressed by DHT treatment and reduction of androgen levels by surgical castration promoted cancer cell growth in an in vivo xenograft model. Tryptophan hydroxylase 1 (TPH1), the rate limit enzyme in serotonin synthesis, was one of the genes which expression was reduced in DHT-treated SE cells. TPH1 was highly expressed in SE cancer tissues compared with adjacent normal tissues. Activation of androgen/AR signaling in SE cells reduced the expression of TPH1 in SE cells, followed by the reduction of serotonin secretion in cell culture supernatant. These results suggested that silencing of androgen/AR signaling may cause initiation and progression of SE through increase in TPH1 gene expression level.

Original languageEnglish (US)
Pages (from-to)35224-35232
Number of pages9
JournalOncotarget
Volume7
Issue number23
DOIs
StatePublished - Jun 7 2016

Keywords

  • Androgen
  • Androgen receptor
  • Seminoma
  • Testicular cancer
  • Tryptophan hydroxylase 1

ASJC Scopus subject areas

  • Oncology

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