Overexpression of Sp1 transcription factor induces apoptosis
Overexpression of Sp1 transcription factor induces apoptosis
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DOI：
10.1038/sj.onc.1209696
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发表时间：
2006-11-09
期刊：
影响因子：
8
通讯作者：
Leverrier, Y.
中科院分区：
文献类型：
--
作者：
Deniaud, E.;Baguet, J.;Leverrier, Y.
转录因子Sp1最近被证明在一些人类癌症中过表达，它的过度表达有助于恶性转化。SP1调控多种基因的表达，参与肿瘤发生的多个方面，如血管生成、细胞生长和抗凋亡等。为了更好地了解Sp1水平升高在细胞凋亡调控中的作用，我们使用逆转录病毒在造血细胞Baf-3和3T3成纤维细胞中过表达该蛋白。我们还使用可诱导表达系统来控制不同细胞类型中异位Sp1的水平。令人惊讶的是，Sp1的过度表达本身在所有被测试的细胞模型中都会诱导细胞凋亡。Sp1过表达诱导的细胞凋亡途径是细胞类型特异性的。最后，使用Sp1的截断形式，我们证明了Sp1诱导的细胞凋亡需要它的DNA结合域。我们的结果强调，未转化细胞中的Sp1水平必须受到严格的调控，因为Sp1的过度表达会导致细胞凋亡。我们的结果还表明，过表达Sp1的癌细胞可以避免Sp1诱导的细胞凋亡。
Transcription factor Sp1 has recently been shown to be overexpressed in a number of human cancers and its overexpression contributes to malignant transformation. Sp1 regulates the expression of a number of genes participating in multiple aspects of tumorigenesis such as angiogenesis, cell growth and apoptosis resistance. To better understand the role of increased Sp1 levels on apoptosis regulation we have used retroviruses to overexpress this protein in haematopoietic Baf-3 cells and in 3T3 fibroblasts. We have also used inducible expression systems to control ectopic Sp1 levels in different cell types. Surprisingly, Sp1 overexpression on its own induces apoptosis in all the cellular models tested. The apoptotic pathways induced by Sp1 overexpression are cell type specific. Finally, using a truncated form of Sp1, we show that Sp1-induced apoptosis requires its DNA-binding domain. Our results highlight that Sp1 levels in untransformed cells must be tightly regulated as Sp1 overexpression leads to the induction of apoptosis. Our results also suggest that cancer cells overexpressing Sp1 can avoid Sp1-induced apoptosis.