Androgen suppresses testicular cancer cell growth<i>in vitro</i>and<i>in vivo</i>

Abstract

// Hideo Nakagawa 1 , Takashi Ueda 1 , Saya Ito 1 , Takumi Shiraishi 1 , Hidefumi Taniguchi 1 , Naruhiro Kayukawa 1 , Hiroyuki Nakanishi 1 , So Ushijima 1 , Motohiro Kanazawa 1 , Terukazu Nakamura 1 , Yoshio Naya 1 , Fumiya Hongo 1 , Kazumi Kamoi 1 , Koji Okihara 1 , Osamu Ukimura 1 1 Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan Correspondence to: Takashi Ueda, e-mail: t-ueda@koto.kpu-m.ac.jp Keywords: androgen, androgen receptor, testicular cancer, seminoma, tryptophan hydroxylase 1 Received: December 02, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: April 11, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: April 29, 2016 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.