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    Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/335


    Title: 血清素運輸體於肺癌之研究
    The Study of Serotonin Transporter in Lung Cancer
    Authors: 林士惟
    Shi-wei Lin
    Contributors: 中山醫學大學:醫學分子毒理學研究所
    柯俊良
    Keywords: 血清素運輸體
    非小細胞肺癌
    肺癌預後
    發炎
    缺氧
    抑癌基因
    Serotonin Transporter
    NSCLC
    prognosis
    inflammation
    hypoxic
    tumor suppressor gene
    Date: 2008/06/16
    Issue Date: 2009-12-18T03:09:01Z (UTC)
    Abstract: 血清素運輸體(Serotonin Transporter, SERT)位於染色體17q11.1- q12,目前已知主要的生理功能是將細胞外的血清素(5HT)轉運回神經細胞末端,使血清素(5HT)在神經細胞內氧化分解或重新儲存回囊泡之中,以調控血清素(5HT)在神經突觸間的傳導;臨床上廣為使用的治療憂鬱症藥物-百憂解(Fluoxetine),即為最著名的血清素運輸體(SERT)的抑制劑,特稱為血清素回收抑制劑(Selective Serotonin Reuptake Inhibitor, SSRI),可影響人類的情緒、情感、睡眠和食慾,因此傳統的相關研究多集中於腦部的血清素運輸體(SERT);本篇是少數研究血清素運輸體(SERT)和癌症相關的論文。本研究以RT-PCR與Real-time PCR分析正常肺細胞株(MRC-5與Beas-2B)與肺癌細胞株(H1299、A549、Calu-1、CH27、H23、CL 1-1與CL 1-5),及18位肺癌病患檢體與旁邊非腫瘤部分,血清素運輸體(SERT) mRNA的表現;並以免疫組織化學染色法(Immunohistochemical staining, IHC),檢視66位肺癌病患檢體的切片,分析血清素運輸體(SERT)表現與肺癌患者存活率之間的相關性。結果顯示,不論是正常肺細胞株(MRC-5與Beas-2B)與肺癌細胞株(H1299、A549、Calu-1、CH27、H23、CL 1-1與CL 1-5)均有SERT的表現,且在18位肺癌病患檢體中肺癌細胞的SERT基因表現量明顯比周邊正常肺細胞來得低;而若將66位NSCLC肺癌病患區分為SERT高表現組和低表現組後統計分析,可發現肺癌病患若為SERT低表現組,其總生存期會較短;尤其在肺腺癌(lung adenocarcinoma)第一期的病患。由此可知血清素運輸體(SERT)在肺部組織的角色極有可能為抑癌基因(tumor suppressor gene),而其在肺部的運作則有待進一步的研究。
    Serotonin Transporter (SERT) is located in the chromosome 17q 11.1-q12. The main biological function is responsible for reuptake of synaptic Serotonin (5HT) to neural terminals. Then, oxidation or restoration of Serotonin (5HT) is happened in neural cells to regulating the transmission of synaptic Serotonin (5HT). The popular antidepressant drug- Prozac (Fluoxetine) is the most famous Selective Serotonin Reuptake Inhibitor (SSRI). It is involved in the regulation of the mood、emotion、sleep and appetite in human being. And so, the traditional researches about Serotonin Transporters (SERTs) were focused on brain. But, our report was focused on cancer as a novel view. By using RT-PCR and Real time-PCR, we found that SERT expressed both in lung cancer cells (H1299、A549、Calu-1、CH27、H23、CL 1-1 and CL 1-5) and normal lung cells (MRC-5 and Beas-2B). In 18 NSCLC patients, expression level of SERT mRNA, analyzed by Real time-PCR, in lung tumor tissue was significantly lower than adjacent normal tissue. Moreover, we studied SERT protein expression in frozen specimens of lung-cancer tissue from 66 randomly selected patients who had undergone surgical resection of NSCLC and evaluated the association between the level of expression and survival. Poor prognosis is associated with the lower expression of SERT protein in lung tumor tissue. Our SERT protein expression is closely associated with the overall survival especially among the stage I disease and adenocarcinoma of the NSCLC patients. Therefore, the results of this study suggest that Serotonin Transporter (SERT) in lung is highly suspected of tumor suppressor gene.
    URI: http://140.128.138.153:8080/handle/310902500/335
    Appears in Collections:[醫學分子毒理學研究所] 博碩士論文

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