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Cell Rep:PTEN基因特定区域可抑制肿瘤

2014-03-25 佚名 健康报

北京大学基础医学院尹玉新教授课题组研究发现,PTEN基因特定区域在维持基因组稳定性,抑制肿瘤发生发展中具有重要作用。相关研究论文日前发表在《细胞》杂志新子刊《细胞报告》上。 尹玉新介绍,PTEN基因是人类肿瘤中突变率仅次于p53(抗癌基因)的强大抗癌基因,在多种类型的癌症中都存在PTEN基因突变或缺失。PTEN突变或表达异常与癌细胞的生长、黏附、迁移、浸润等密切相关

北京大学基础医学院尹玉新教授课题组研究发现,PTEN基因特定区域在维持基因组稳定性,抑制肿瘤发生发展中具有重要作用。相关研究论文日前发表在《细胞》杂志新子刊《细胞报告》上。

尹玉新介绍,PTEN基因是人类肿瘤中突变率仅次于p53(抗癌基因)的强大抗癌基因,在多种类型的癌症中都存在PTEN基因突变或缺失。PTEN突变或表达异常与癌细胞的生长、黏附、迁移、浸润等密切相关,这表明PTEN在控制肿瘤发生、发展过程中发挥着重要的作用。大量研究已经证实,PTEN N端结构可通过抑制PI3K/AKT信号通路,调控细胞存活和细胞增殖,但对于PTEN C端的功能却了解甚少。尹玉新团队以往的研究发现C端区域是PTEN维持染色体完整性的必要结构,而实体肿瘤中大量突变发生于PTEN C端,也表明这一区域有可能在肿瘤抑制中起着重要的作用。

在该研究中,尹玉新团队构建了一种PTEN基因末端缺失小鼠模型。病理分析显示,PTEN C端区域缺失小鼠形成了多种自发性肿瘤,包括一些上皮肿瘤,如乳腺癌、甲状腺癌等,并且首次发现B细胞淋巴瘤。进一步研究发现,PTEN C端区域缺失会导致基因组不稳定和常见脆性位点重排,可能是肿瘤发生的遗传基础。令人惊奇的是,PTEN C端缺失会诱导p53表达并激活其下游靶基因,而同时敲除p53则会促进肿瘤转移但不会影响肿瘤发生,表明p53主要作用在于抑制肿瘤发展,而不是肿瘤的发生。

该研究首次证实PTEN C端在维持基因组稳定和抑制肿瘤发生过程中发挥了至关重要的作用,并且揭示抗癌基因PTEN和p53 的网状联系和协同作用。这些发现可能会为PTEN、p53在肿瘤靶向个体化治疗的选择与应用上提供新的理论依据。

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    2015-02-22 维他命
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    2014-03-27 xiaogang317
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    2014-03-26 lele033086

    PTEN,我很关注

    0

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Baidu
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Baidu
map
Baidu
map