Defective heat shock factor 1 inhibits the growth of fibrosarcoma derived from simian virus 40/T antigen‑transformed MEF cells.
Defective heat shock factor 1 inhibits the growth of fibrosarcoma derived from simian virus 40/T antigen‑transformed MEF cells.
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有缺陷的热休克因子1抑制猿猴病毒40/T抗原转化的MEF细胞来源的纤维肉瘤的生长
DOI：
10.3892/mmr.2015.4300
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发表时间：
2015-11
影响因子：
3.4
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Jiang Q;Zhang Z;Li S;Wang Z;Ma Y;Hu Y
热休克因子1 （Hsf1）在体外调节人肿瘤细胞系的增殖和某些小鼠模型的组织特异性肿瘤发生中起重要作用。然而，其在病毒肿瘤发生中的作用仍有待充分阐明。在本研究中，研究Hsf1在猴病毒40/T抗原（SV40/TAG）转化小鼠胚胎成纤维细胞（MEF）细胞系成纤维细胞瘤中的作用。敲除Hsf1抑制MEF细胞的体外增殖和裸鼠体内成纤维细胞瘤的生长和肺转移。敲除Hsf1后，p53和磷酸化视网膜母细胞瘤蛋白（pRb）的蛋白表达水平升高，而热休克蛋白25 （Hsp25）的表达降低，血管生成标志物血管内皮生长因子、分化簇34和因子VIII相关抗原的表达也降低。此外，免疫沉淀表明敲除Hsf1可抑制SV40/TAG与p53或pRb的关联。这些数据表明，Hsf1通过调节SV40/TAG与肿瘤抑制因子p53和pRb之间的关联，参与了SV40/TAG衍生的成纤维细胞瘤生长和转移的调控。目前的研究进一步证明Hsf1可能是治疗癌症的一个新的治疗靶点。
Heat shock factor 1 (Hsf1) serves an important role in regulating the proliferation of human tumor cell lines in vitro and tissue specific tumorigenesis in certain mouse models. However, its role in viral-oncogenesis remains to be fully elucidated. In the current study, the role of Hsf1 in fibroblastoma derived from simian virus 40/T antigen (SV40/TAG)-transformed mouse embryonic fibroblast (MEF) cell lines was investigated. Knockout of Hsf1 inhibited MEF cell proliferation in vitro and fibroblastoma growth and metastasis to the lungs in vivo in nude mice. Knockout of Hsf1 increased the protein expression levels of p53 and phosphorylated retinoblastoma protein (pRb), however reduced the expression of heat shock protein 25 (Hsp25) in addition to the expression of the angiogenesis markers vascular endothelial growth factor, cluster of differentiation 34 and factor VIII related antigen. Furthermore, immunoprecipitation indicated that knockout of Hsf1 inhibited the association between SV40/TAG and p53 or pRb. These data suggest that Hsf1 is involved in the regulation of SV40/TAG-derived fibroblastoma growth and metastasis by modulating the association between SV40/TAG and tumor suppressor p53 and pRb. The current study provides further evidence that Hsf1 may be a novel therapeutic target in the treatment of cancer.