Inactivation of the tumor suppressor Krüppel-like factor 6 (KLF6) by mutation or decreased expression in hepatocellular carcinomas
| Autor: | Feng Chen, Zhi Chen, Han-yin Jin, Xiao-yan Xu, Xiao-hong Chen, Xiu-cheng Pan |
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| Rok vydání: | 2006 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Carcinoma Hepatocellular Tumor suppressor gene Blotting Western Mutant Kruppel-Like Transcription Factors Biology Transfection medicine.disease_cause General Biochemistry Genetics and Molecular Biology Loss of heterozygosity Cell Line Tumor Proto-Oncogene Proteins Gene expression Kruppel-Like Factor 6 medicine Humans RNA Messenger General Pharmacology Toxicology and Pharmaceutics neoplasms Mutation General Veterinary Reverse Transcriptase Polymerase Chain Reaction Cell Cycle Liver Neoplasms Sequence Analysis DNA General Medicine Cell cycle Molecular biology digestive system diseases Gene Expression Regulation Neoplastic Blot Biomedicine KLF6 Cancer research |
| Zdroj: | Journal of Zhejiang University SCIENCE B. 7:830-836 |
| ISSN: | 1862-1783 1673-1581 |
| DOI: | 10.1631/jzus.2006.b0830 |
| Popis: | Background and aim: The Krüppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of heterozygosity (LOH). However, there is no data reporting the levels of KLF6 both mRNA and protein in hepatocellular carcinomas (HCCs). We therefore detected mutations and expression of KLF6 in HCC tissues and further observed the effect of it on cell growth in HCC cell lines. Methods: We analyzed the exon-2 of KLF6 gene by direct DNA sequencing, and detected the expression of KLF6 by RT-PCR and Western blot in 23 HCC tissues and corresponding nontumorous tissues. Loss of growth suppressive effect of the HCC-derived KLF6 mutant was characterized by in vitro growth curves plotted, flow cytometry and Western blotting. Results: KLF6 mutations were found in 2 of 23 HCC tissues and one of mutations was missense. Expression of KLF6 mRNA or protein was down-regulated in 8 (34.7%) or 9 (39.1%) of 23 HCC tissues. Wild-type KLF6 (wtKLF6) inhibited cellular proliferation and prolonged G1-S transition by inducing the expression of p21WAF1 following stable transfection into cultured HepG2 cells, but tumor-derived KLF6 mutant (mKLF6) had no effects. Conclusion: Our findings suggest that KLF6 may be involved in pathogenesis of HCC. |
| Databáze: | OpenAIRE |
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