title: Modulation of human serotonin transporter expression by 5-HTTLPR in colon cells.
abstract: Serotonin (5-HT) is a monoamine neurotransmitter and plays important roles in several of the human body's systems. Known as a primary target for psychoactive drug development, the 5-HT transporter (5-HTT, SERT) plays a critical role in the regulation of serotonergic function by reuptaking 5-HT. The allelic variation of 5-HTT expression is caused by functional gene promoter polymorphism with two principal variant alleles, 5-HTT gene-linked polymorphic region (5-HTTLPR). It has been demonstrated that 5-HTTLPR is associated with numerous neuropsychiatric disorders. The functional roles of 5-HTTLPR have been reported in human choriocarcinoma (JAR), lymphoblast and raphe cells. To date, the significance of 5-HTTLPR in gastrointestinal tract-derived cells has never been elucidated. Thus, the impact of 5-HTTLPR on 5-HTT transcription was studied in SW480 human colon carcinoma cells, which were shown to express 5-HTT. We found 42-bp fragment in long (L) allele as compared to short (S) allele, and this allelic difference resulted in 2-fold higher transcriptional efficiency of L allele (P < 0.05) as demonstrated using a functional reporter gene assay. Nevertheless, the transcriptional effect of estrogen and glucocorticoid on 5-HTT expression via 5-HTTLPR was not found in this cell line. Our study was the first to demonstrate the molecular role of this allelic variation in gastrointestinal tract cells.
authors.affiliation: Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand; E-Mail:  anchalee.pssl@gmail.com.
authors.forename: Anchalee
authors.initials: A
authors.lastname: Prasansuklab
authors.forename: Yong
authors.initials: Y
authors.lastname: Poovorawan
authors.forename: Tewin
authors.initials: T
authors.lastname: Tencomnao
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D013256:Steroids; D014157:Transcription Factors
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