title: Androgen suppresses testicular cancer cell growth in vitro and in vivo.
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.
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Saya
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Shiraishi
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Naruhiro
authors.initials: N
authors.lastname: Kayukawa
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: So
authors.initials: S
authors.lastname: Ushijima
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kanazawa
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Terukazu
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Naya
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Hongo
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kamoi
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Okihara
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ukimura
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011944:Receptors, Androgen / Q000378:metabolism*; D018239:Seminoma / Q000473:pathology*; D013736:Testicular Neoplasms / Q000473:pathology*; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis*
chemical_list: C410798:AR protein, human; D000728:Androgens; D011944:Receptors, Androgen; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase
keywords: androgen; androgen receptor; seminoma; testicular cancer; tryptophan hydroxylase 1