KLF6 通过下调 PTTG1 癌基因发挥肿瘤抑制活性。
Tumor suppressor activity of KLF6 mediated by downregulation of the PTTG1 oncogene.
机构信息
Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
出版信息
FEBS Lett. 2010 Mar 5;584(5):1006-10. doi: 10.1016/j.febslet.2010.01.049. Epub 2010 Jan 30.
Abstract
The tumor suppressor Kruppel-like factor 6 (KLF6) is frequently inactivated in hepatocellular carcinoma (HCC). To unearth downstream transcriptional targets of KLF6, cDNA microarray analysis of whole liver was compared between KLF6+/+ and KLF6+/- mice. Pituitary tumor transforming gene 1 (PTTG1), an oncogene, was the most up-regulated transcript in KLF6+/- liver. In human HCCs, KLF6 mRNA was significantly decreased, associated with increased PTTG1. In HepG2, KLF6 transcriptionally repressed PTTG1 by direct promoter interaction. Whereas KLF6 downregulation by siRNA increased HepG2 proliferation, siRNA to PTTG1 was anti-proliferative. PTTG1 downregulation represents a novel tumor suppressor pathway of KLF6.
摘要
肿瘤抑制因子 Kruppel 样因子 6（KLF6）在肝细胞癌（HCC）中经常失活。为了揭示 KLF6 的下游转录靶标，对 KLF6+/+ 和 KLF6+/- 小鼠的整个肝脏进行了 cDNA 微阵列分析。垂体肿瘤转化基因 1（PTTG1）是一种癌基因，在 KLF6+/- 肝脏中是上调最明显的转录本。在人 HCC 中，KLF6mRNA 显著降低，与 PTTG1 增加相关。在 HepG2 中，KLF6 通过直接启动子相互作用转录抑制 PTTG1。而 KLF6 的 siRNA 下调会增加 HepG2 的增殖，而 PTTG1 的 siRNA 则具有抗增殖作用。PTTG1 下调代表 KLF6 的一种新的肿瘤抑制途径。
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