The role of serotonin and serotonin receptor subtype 2c in an in vitro model of prostate cancer
Eldahshan, Wael Salem Abdelhameed
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Focal neuroendocrine differentiation is frequently observed in prostate cancer after long-term anti-androgen treatment, and is accompanied by aggressive disease and poor prognosis. Serotonin (5-hydroxytryptamine or 5-HT), among other factors, is secreted by neuroendocrine cells to modify the tumor micro-environment. Serotonin is a well-known neurotransmitter that is secreted in various tissues such as the central nervous system and the gastrointestinal tract and performs multiple functions in our body. Different 5-HT receptors have been shown to be expressed in prostate cancer such as HTR1A, 1B, 1D, 2B, and 4. Our preliminary data suggests that serotonin receptor 2C (HTR2C) is expressed in some prostate cancer cell lines and is playing a role in prostate cancer. The serotonin receptor 2C is a G-protein coupled receptor (GPCR) that is predominantly found in the choroid plexus among other brain areas. The pre-mRNA of HTR2C undergoes extensive editing by adenosine deaminase acting on RNA enzymes (ADAR). This editing can change the protein sequence, structure and function of the HTR2C receptor. In the current study, HTR2C activity is characterized using a specific inhibitor (SB242,084) in two of the commonly used androgen-independent cell lines: PC3 and LNCaP C4-2. Our data shows that HTR2C inhibition decreases cell viability and cell motility in PC3 cells and in LNCaP C4-2 cells, HTR2C inhibition decreased cell viability, decreased cell diameter and circularity and induced a change in cell shape. In future experiments we aim to knockdown the HTR2C receptor in order to confirm the effects of SB242,084 on PCa cell lines is through HTR2C receptor. Furthermore, we aim to study the mechanism of the anticancer effect of HTR2C inhibition. A better understanding of the HTR2C editing and signaling will aid in the development of new drugs that specifically target aggressive forms of prostate cancer.