Serotonin receptor 4 (5-HTR4) regulates expression of ER beta (ERβ) and cell growth in human prostate cancer

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 292-325-Breast & Prostate Cancer
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-324
Yasuhiro Nakamura*, Kazue Ise, Saulo JA Felizola, Keely M McNamara and Hironobu Sasano
Tohoku University Graduate School of Medicine, Sendai, Japan
Background: Androgens are well known to play important roles in the pathogenesis of prostate cancer via androgen receptor (AR). Estrogens have been also recently proposed as potential agents in the development and progression of prostate cancer via estrogen receptor (ER), mainly ER beta (ERβ). The development of hormone-refractory prostate cancer (HRPC) is generally associated with aggressive biological behavior and has emerged as one of the most serious clinical problems in the long-term management of the patients with prostate cancer. Increased expression of serotonin (5-HT) receptor, especially type 4 (5-HTR4), has been proposed to be involved in autocrine/paracrine mechanisms of HRPC and peritumoral mast cells have been known to be histopatohologically present abundantly but their clinical and biological significance in human prostate cancer has remained largely unknown.

Experimental design: We evaluated the status of 5-HTR4 in 112 human prostate cancer cases using immunohistochemistry and correlated the findings with clinicopathological features of the patients and the expression levels of AR and ERβ. In order to further analyze its underlying mechanism, androgen-dependent human prostate cancer cell line (LNCaP) expressing 5-HTR4 was treated by 5-HTR4 agonist.

Results: 5-HTR4 immunoreactivity was detected in 34% cases of prostate cancer (38/112). 5-HTR4 immunoreactivity was significantly correlated with that of ERβ but not with AR. 5-HT immunorectivity was not detected in carcinoma cells, but peritumoral mast cells, a potential site of serotonin production, were abundant within the tissues. Results of in vitro experiments using LNCaP prostate carcinoma cell line demonstrated that 24h incubation with 5-HTR4 agonist (10nM) increased the expression level of ERβ mRNA compared to controls but 48h incubation with 5-HTR4 agonist (10nM) significantly inhibited carcinoma cell proliferation.

Conclusion: Results of our present study indicated that 5-HTR4 is involved in the regulation of cell proliferation and of ERβ expression in human prostate carcinoma cells possibly through 5-HT secreted by peritumoral mast cells.

Nothing to Disclose: YN, KI, SJF, KMM, HS

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