TSC2 epigenetic defect in primary LAM cells. Evidence of an anchorage-independent survival.
TSC2 epigenetic defect in primary LAM cells. Evidence of an anchorage-independent survival.
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原代 LAM 细胞中的 TSC2 表观遗传缺陷。不依赖锚地生存的证据。
DOI：
10.1111/jcmm.12237
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发表时间：
2014-05
影响因子：
5.3
通讯作者：
Gorio A
中科院分区：
文献类型：
--
作者：
Lesma E;Ancona S;Sirchia SM;Orpianesi E;Grande V;Colapietro P;Chiaramonte E;Di Giulio AM;Gorio A
多发性硬化症（TSC）是由TSC 1或TSC 2基因突变引起的。淋巴管平滑肌瘤病（LAM）可以是散发性的或与TSC相关，其特征是异常α平滑肌（ASM）样细胞的广泛肺增殖。我们研究了从患有与TSC相关的LAM的患者的乳糜胸中分离的ASM细胞的特征，命名为LAM/TSC细胞，其具有生殖系TSC 2突变和导致缺乏结核菌素的表观遗传缺陷。LAM/TSC细胞的增殖是表皮生长因子（EGF）依赖性的，并且EGF受体的阻断导致细胞死亡，如我们先前在缺乏tuberin的细胞中所示。LAM/TSC细胞自发分离可能是因为粘着斑激酶（FAK）/Akt/mTOR通路失活，并显示出独立于粘附的存活能力。非粘附性LAM/TSC细胞显示出与肿瘤干细胞特征一致的极低增殖率。此外，LAM/TSC细胞具有干细胞特性，并分泌大量的白细胞介素（IL）-6和IL-8。抗EGF受体抗体和雷帕霉素影响非贴壁细胞的增殖和活力。总之，LAM/TSC细胞特征的理解是重要的，在LAM和TSC的细胞侵袭性的评估，并应提供一个有用的模型来测试治疗方法，旨在控制其迁移能力。
Tuberous sclerosis complex (TSC) is caused by mutations in TSC1 or TSC2 genes. Lymphangioleiomyomatosis (LAM) can be sporadic or associated with TSC and is characterized by widespread pulmonary proliferation of abnormal α-smooth muscle (ASM)-like cells. We investigated the features of ASM cells isolated from chylous thorax of a patient affected by LAM associated with TSC, named LAM/TSC cells, bearing a germline TSC2 mutation and an epigenetic defect causing the absence of tuberin. Proliferation of LAM/TSC cells is epidermal growth factor (EGF)-dependent and blockade of EGF receptor causes cell death as we previously showed in cells lacking tuberin. LAM/TSC cells spontaneously detach probably for the inactivation of the focal adhesion kinase (FAK)/Akt/mTOR pathway and display the ability to survive independently from adhesion. Non-adherent LAM/TSC cells show an extremely low proliferation rate consistent with tumour stem-cell characteristics. Moreover, LAM/TSC cells bear characteristics of stemness and secrete high amount of interleukin (IL)-6 and IL-8. Anti-EGF receptor antibodies and rapamycin affect proliferation and viability of non-adherent cells. In conclusion, the understanding of LAM/TSC cell features is important in the assessment of cell invasiveness in LAM and TSC and should provide a useful model to test therapeutic approaches aimed at controlling their migratory ability.
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影响因子：
24.3
作者：
Johnson, SR
通讯作者：
Johnson, SR
影响因子：
6
作者：
Karbowniczek, M;Yu, J;Henske, EP
通讯作者：
Henske, EP
DOI：
10.1124/jpet.107.123679
发表时间：
2007-09-01
影响因子：
3.5
作者：
Gorio, Alfredo;Madaschi, Laura;Di Giulio, Anna Maria
通讯作者：
Di Giulio, Anna Maria
影响因子：
6
作者：
Giri, D;Ozen, M;Ittmann, M
通讯作者：
Ittmann, M
影响因子：
9.6
作者：
Cai, Xiong;Pacheco-Rodriguez, Gustavo;Moss, Joel
通讯作者：
Moss, Joel