Taipei Medical University Institutional Repository:Item 987654321/813
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    题名: Studies on the Potential Molecular Mechanisms of Nicotinic Receptors-mediated Carcinogenic Effects in Human Breast Cancer Cells
    作者: 吳志雄
    Wu CH;Ho YS
    贡献者: 外科學科
    日期: 2008
    上传时间: 2009-08-13 14:46:31 (UTC+8)
    摘要: Tobacco-smoking is one of the well understanding
    carcinogenic factors involved in breast cancer formation. In this
    study, we first demonstrated that the several types of nicotinic
    acetylcholine receptors (nAchRs) were detected in breast
    cancer cell lines including MCF-7 and MDA-MB-231. The
    expression of the nAchR mRNA levels in tumor tissues from
    157 cases of breast cancer patients in Taiwan were determined
    and found that the α5, α9 and α10 subunits of the nAchRs were
    the most prevalence in both normal and tumor tissue.
    Quantitative assays of the nAchRs mRNA levels was performed
    by real-time PCR analysis which revealed that the expression
    levels of 9-nAchR was higher in most of the tumor tissue when
    compared to the normal tissues which dissected form the tumor
    margin. The receptor binding activity assay was performed and
    demonstrated that 9-nAchR significant binding to its ligand
    (nicotine) in a concentration as low as 7 M and reached the
    maximal level as soon as 60 minutes. The 9-nAchR
    expression in breast cancer cells was knock-downed by SiRNA
    technique and demonstrated that Akt-p (ser473) signaling
    regulatory pathways play an important role in nicotine-mediated
    breast cancer cells proliferation. We further demonstrated that
    the -9-nAchR expression was significant upregulated in the
    promoter level by nicotine and sex hormone (estradiol, E2) as
    evidenced by luciferase reporter assay. Our results further
    demonstrated that E2-mediated nAchR expression was through
    activation of the estrogen receptor (ER) as demonstrated by
    chromatin immunoprecipitation analysis. In vivo study was
    performed by nude mice model and demonstrated that the 9-
    nAchR-mediated cancer cell proliferation may play a major role
    in response to nicotine-induced breast tumor formation. Such
    results implied that 9-nAchR and its cooperative role with sex
    hormone (such as E2) may be significant in nicotine-mediated
    breast tumor carcinogenesis
    關聯: BIT Life Sciences 1st Annual World Cancer Congress 2008, Shanghai, China
    数据类型: conference
    显示于类别:[外科學科] 會議論文

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