Wang Shaoping, Kang Lili, Chen Xiaoping, Zhou Hejun
Department of Hepatobiliary Surgery, Futian People's Hospital, Shenzhen, 518033, China.
J Huazhong Univ Sci Technolog Med Sci. 2010 Aug;30(4):470-6. doi: 10.1007/s11596-010-0451-3. Epub 2010 Aug 17.
Kruppel-like factor 6 (KLF6) was reported as tumor suppressor in multiple cancers. However, loss of chromosomal locus spanning KLF6 is relatively infrequent in previous published studies. To explore the role of KLF6 in hepatocellular carcinoma (HCC), we examined the gene for expression change, loss of heterozygosity (LOH) and mutation in 26 HCC samples. The expression levels of KLF6 were significantly down-regulated in HCCs, as detected by qRT-PCR. LOH occurred in 11 (52%) of 21 tumors, and all the samples with LOH showed KLF6 down-regulation. The mutational frequency was 24%, and sequence changes located in activation domain of KLF6. Furthermore, MTT assay showed a significant antiproliferative effect of the wt KLF6 transfected in HepG2 hepatoblastoma cells. Fluorescence-activated cell sorting analysis revealed that KLF6 could induce apoptosis. These findings indicate that deregulation of KLF6, together with genetic abnormalities of allelic imbalance and mutations, may play a role in HCC pathogenesis.
Kruppel样因子6（KLF6）在多种癌症中被报道为肿瘤抑制因子。然而，在先前发表的研究中，跨越KLF6的染色体位点缺失相对不常见。为了探究KLF6在肝细胞癌（HCC）中的作用，我们检测了26例HCC样本中该基因的表达变化、杂合性缺失（LOH）及突变情况。通过qRT-PCR检测发现，HCC中KLF6的表达水平显著下调。21例肿瘤中有11例（52%）发生了LOH，所有发生LOH的样本均显示KLF6下调。突变频率为24%，序列变化位于KLF6的激活域。此外，MTT分析显示，在HepG2肝母细胞瘤细胞中转染野生型KLF6具有显著的抗增殖作用。荧光激活细胞分选分析表明，KLF6可诱导细胞凋亡。这些发现表明，KLF6的失调以及等位基因失衡和突变等基因异常可能在HCC发病机制中发挥作用。
