SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance.
SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance.
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DOI：
10.7150/ijbs.6.806
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发表时间：
2010-12-15
影响因子：
9.2
通讯作者：
Zheng ZM
中科院分区：
文献类型：
--
作者：
Jia R;Li C;McCoy JP;Deng CX;Zheng ZM
肿瘤细胞显示出与正常细胞不同的基因表达谱。细胞剪接因子水平的扰动可以改变基因表达，可能导致肿瘤发生。我们发现剪接因子SRp 20（SFRS 3）在癌症中高度表达。SRp 20调节叉头盒转录因子M1（FoxM 1）及其两个转录靶点PLK 1和Cdc 25 B的表达，并控制细胞周期进程和增殖。RNAi介导的SRp 20表达降低的癌细胞表现出G2/M期阻滞、生长迟缓和凋亡。在啮齿动物成纤维细胞中增加SRp 20表达促进永生细胞生长和转化。更重要的是，我们发现SRp 20促进了裸鼠肿瘤诱导和肿瘤生长的维持，并使永生啮齿动物成纤维细胞致瘤。总的来说，这些结果表明肿瘤细胞中SRp 20表达的增加是肿瘤发生、进展和维持的关键步骤。
Tumor cells display a different profile of gene expression than their normal counterparts. Perturbations in the levels of cellular splicing factors can alter gene expression, potentially leading to tumorigenesis. We found that splicing factor SRp20 (SFRS3) is highly expressed in cancers. SRp20 regulated the expression of Forkhead box transcription factor M1 (FoxM1) and two of its transcriptional targets, PLK1 and Cdc25B, and controlled cell cycle progression and proliferation. Cancer cells with RNAi-mediated reduction of SRp20 expression exhibited G2/M arrest, growth retardation, and apoptosis. Increased SRp20 expression in rodent fibroblasts promoted immortal cell growth and transformation. More importantly, we found that SRp20 promoted tumor induction and the maintenance of tumor growth in nude mice and rendered immortal rodent fibroblasts tumorigenic. Collectively, these results suggest that increased SRp20 expression in tumor cells is a critical step for tumor initiation, progression, and maintenance.