ST2 gene products critically contribute to cellular transformation caused by an oncogenic Ras mutant.
ST2 gene products critically contribute to cellular transformation caused by an oncogenic Ras mutant.
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DOI：
10.1016/j.heliyon.2017.e00436
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发表时间：
2017-10
期刊：
影响因子：
4
通讯作者：
Yanagisawa K
中科院分区：
文献类型：
--
作者：
Tago K;Ohta S;Kashiwada M;Funakoshi-Tago M;Matsugi J;Tominaga SI;Yanagisawa K
ST 2基因最初被鉴定为初级应答基因，其基因产物的表达由生长因子刺激和致癌应激诱导。在本研究中，我们观察到致癌Ras突变体诱导ST 2和ST 2L蛋白的表达。有趣的是，ST 2基因产物在NIH-3 T3鼠成纤维细胞中的强制表达显著增强Ras（G12 V）诱导的细胞转化。此外，当通过RNA干扰技术沉默ST 2基因产物的表达时，Ras（G12 V）诱导的细胞转化被显著抑制。根据这些观察，表明致癌Ras诱导的ST 2基因产物的表达是加速细胞转化所必需的，并且这似乎与ST 2/ST 2L的配体IL-33的刺激无关。有趣的是，ST 2基因产物的敲除导致转化的鼠成纤维细胞中Rb磷酸化的减少，表明在细胞转化期间ST 2基因产物在细胞周期进展中的功能参与。我们的研究结果有力地表明了ST 2基因产物在细胞转化中的重要性，以及ST 2基因产物影响细胞转化和细胞增殖的新机制的存在。
The ST2 gene was originally identified as a primary responsive gene, and the expressions of its gene products are induced by stimulation with growth factors and by oncogenic stresses. In this study, we observed that oncogenic Ras mutant induced the expression of ST2 and ST2L proteins. Interestingly, the enforced expression of ST2 gene products in NIH-3T3 murine fibroblasts remarkably enhanced Ras (G12V)-induced cellular transformation. Furthermore, when the expression of ST2 gene products was silenced by RNA-interference technique, Ras (G12V)-induced cellular transformation was drastically suppressed. According to these observations, it was indicated that the oncogenic Ras-induced expression of ST2 gene products is required for the acceleration of cellular transformation, and this seems to be independent of the stimulation with IL-33, a ligand for ST2/ST2L. Interestingly, knockdown of ST2 gene products caused a reduction in Rb phosphorylation in transformed murine fibroblasts, suggesting the functional involvement of ST2 gene products in cell cycle progression during cellular transformation. Our current study strongly suggests the importance of ST2 gene products in cellular transformation, and the presence of novel mechanism how ST2 gene products affect the cellular transformation and cell proliferation.