Loss of cellular adhesion to matrix induces p53-independent expression of PTEN tumor suppressor.
Loss of cellular adhesion to matrix induces p53-independent expression of PTEN tumor suppressor.
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DOI：
10.1186/1471-2199-3-11
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发表时间：
2002-07-12
影响因子：
--
通讯作者：
Schönthal AH
中科院分区：
文献类型：
--
作者：
Wu RC;Blumenthal M;Li X;Schönthal AH
已发现肿瘤抑制基因 PTEN 在多种晚期肿瘤中发生突变。当引入缺乏该基因野生型等位基因的肿瘤细胞时，外源性 PTEN 能够抑制其独立贴壁生长的能力，从而恢复肿瘤细胞的典型特征之一。由于这些发现表明 PTEN 可能参与锚定依赖性细胞生长的调节，因此我们分析了具有锚定依赖性表型的非肿瘤细胞中 PTEN 功能的这方面。我们发现，作为对细胞-基质相互作用破坏的反应，内源性 PTEN 的表达被转录激活，并且细胞中 PTEN 蛋白和活性水平升高。这些事件与粘着斑激酶的磷酸化降低相关，甚至在没有 p53（一种肿瘤抑制蛋白和最近建立的 PTEN 转录刺激物）的情况下也会发生。鉴于 PTEN 强大的生长抑制能力，我们得出结论，细胞基质破坏后其诱导有助于维持正常细胞的贴壁依赖性表型。
The tumor suppressor gene PTEN has been found mutated in many types of advanced tumors. When introduced into tumor cells that lack the wild-type allele of the gene, exogenous PTEN was able to suppress their ability to grow anchorage-independently, and thus reverted one of the typical characteristics of tumor cells. As these findings indicated that PTEN might be involved in the regulation of anchorage-dependent cell growth, we analyzed this aspect of PTEN function in non-tumor cells with an anchorage-dependent phenotype. We found that in response to the disruption of cell-matrix interactions, expression of endogenous PTEN was transcriptionally activated, and elevated levels of PTEN protein and activity were present in the cells. These events correlated with decreased phosphorylation of focal adhesion kinase, and occurred even in the absence of p53, a tumor suppressor protein and recently established stimulator of PTEN transcription. In view of PTEN's potent growth-inhibitory capacity, we conclude that its induction after cell-matrix disruptions contributes to the maintenance of the anchorage-dependent phenotype of normal cells.
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DOI：
10.1073/pnas.170290997
发表时间：
2000-08-29
影响因子：
11.1
作者：
Henriet, P;Zhong, ZD;DeClerck, YA
通讯作者：
DeClerck, YA
影响因子：
8
作者：
Kawada, M;Yamagoe, S;Uehara, Y
通讯作者：
Uehara, Y
影响因子：
64.5
作者：
HARPOLD, MM;EVANS, RM;DARNELL, JE
通讯作者：
DARNELL, JE
影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
56.9
作者：
Fang, F;Orend, G;Ruoslahti, E
通讯作者：
Ruoslahti, E