title: Serotonin synthesis and metabolism-related molecules in a human prostate cancer cell line.
abstract: Prostate cancer is one of the most common tumors in males and its incidence is steadily increasing worldwide. Serotonin or 5-hydroxytryptamine (5-HT) is a well-known neurotransmitter that mediates a wide variety of physiological effects. An increase in the number of 5-HT-releasing neuroendocrine (NE) cells has been correlated with tumor progression. However, it is particularly unclear whether released 5-HT or the release of 5-HT has a role in tumor cell growth. We hypothesized that 5-HT synthesis and metabolism in NE cells regulate the growth of prostate cancer cells. In the present study, 5-HT was found to play a role as a cell growth factor in prostate cancer cells. Moreover, the pharmacological inhibition of 5-HT synthesis and metabolism interrupted the growth of prostate cancer cells. To confirm the existence of 5-HT in prostate cancer cells, we performed ELISA, HPLC, RT-PCR and immunohistochemical analyses. A high expression of tryptophan hydroxylase (TPH-1), dopa decarboxylase (DDC) and monoamine oxidase A (MAO-A) was noted in the prostate cancer cells when compared with normal prostate cells. Previous studies showed that 5-HT stimulated the proliferation of prostate cancer cells mediated by 5-HT receptors 5-HTR1A and R1B. However, cell proliferation was significantly inhibited when siRNA for both DDC and TPH-1 was transfected to the cells. Consequently, we propose that the secretion system of prostate NE cells capable of 5-HT synthesis and metabolism plays a significant role in prostate tumor generation and progression. These findings provide crucial clues for the development of potential pharmacotherapeutics to slow prostate tumor progression.
authors.affiliation: Department of Urology, Wakayama Medical University, Wakayama 641-0012.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shinka
authors.forename: Dai
authors.initials: D
authors.lastname: Onodera
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shoji
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Moriuchi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukumoto