Sonier Brigitte, Arseneault Madeleine, Lavigne Carole, Ouellette Rodney J, Vaillancourt Cathy
Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada.
Biochem Biophys Res Commun. 2006 May 19;343(4):1053-9. doi: 10.1016/j.bbrc.2006.03.080. Epub 2006 Mar 24.
Serotonin (5-hydroxytryptamine, 5-HT) has been described as a mitogen in a variety of cell types and carcinomas. It exerts its mitogenic effect by interacting with a wide range of 5-HT receptor types. Certain studies suggest that some selective serotonin re-uptake inhibitors promote breast cancer in animals and humans. This study attempts to clarify the role of serotonin in promoting the growth of neoplastic mammary cells. Expression of the 5-HT(2A) serotoninergic receptor subtype in MCF-7 cells was determined by RT-PCR, Western blotting, and immunofluorescence analysis. The mitogenic effect of 5-HT on MCF-7 cells was determined by means of the MTT proliferation assay. We have demonstrated that the 5-HT(2A) receptor subtype is fully expressed in the MCF-7 human breast cancer cell line, in terms of encoding mRNA and receptor protein. Automated sequencing has confirmed that the 5-HT(2A) receptor present in this cell line is identical to the 5-HT(2A) receptor found in human platelets and in human cerebral cortex. Furthermore, this receptor was found by immunofluorescence to be on the plasma membrane. MTT proliferation assays revealed that 5-HT and DOI, a selective 5-HT(2A) receptor subtype agonist, stimulated MCF-7 cell. These results indicate that 5-HT plays a mitogenic role in neoplastic mammary cells. Our data also indicate that 5-HT exerts this positive growth effect on MCF-7 cells through, in part, the 5-HT(2A) receptor subtype, which is fully expressed in this cell line.
血清素（5-羟色胺，5-HT）在多种细胞类型和癌组织中被描述为一种促细胞分裂剂。它通过与多种5-HT受体类型相互作用发挥其促有丝分裂作用。某些研究表明，一些选择性5-羟色胺再摄取抑制剂在动物和人类中会促进乳腺癌。本研究旨在阐明血清素在促进肿瘤性乳腺细胞生长中的作用。通过逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法和免疫荧光分析来测定MCF-7细胞中5-HT（2A）血清素能受体亚型的表达。通过MTT增殖试验来测定5-HT对MCF-7细胞的促有丝分裂作用。我们已经证明，就编码mRNA和受体蛋白而言，5-HT（2A）受体亚型在MCF-7人乳腺癌细胞系中完全表达。自动测序已证实，该细胞系中存在的5-HT（2A）受体与在人血小板和大脑皮质中发现的5-HT（2A）受体相同。此外，通过免疫荧光发现该受体位于质膜上。MTT增殖试验显示，5-HT和DOI（一种选择性5-HT（2A）受体亚型激动剂）刺激了MCF-7细胞。这些结果表明，5-HT在肿瘤性乳腺细胞中发挥促有丝分裂作用。我们的数据还表明，5-HT对MCF-7细胞的这种正向生长作用部分是通过5-HT（2A）受体亚型发挥的，该受体亚型在该细胞系中完全表达。
