Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

KLF6 (Zf9, COPEB), an ubiquitous transcription factor, maps to chromosome 10p. Recently, KLF6 was found to have a more generalized role in tumorigenesis as a candidate tumor suppressor gene for some tumors. However, results from other published studies seem not to be in agreement with data from previous studies. Gene-expression analysis is increasingly important in biological research. Loss of expression is one of the mechanisms to functionally inactivate a tumor suppressor gene. To investigate the expression change of KLF6 gene associated with HCC as a step toward a better understanding of the molecular pathophysiology, and to provide the basis for analysis of KLF6 gene in HCC carcinogenesis. We analyzed the expression of KLF6 mRNA in 26 samples of HCC tissues and hepatoma cell lines(Hep3B and HepG2) detected by Real-Time quantitative RT-PCR (qRT-PCR) and conventional RT-PCR assay. To confirm and extend the data obtained at RNA level, we performed detailed immunoblotting analysis on HCC tissues and hepatoma cell lines using a rabbit polyclonal antibody specific for KLF6. NKLF6 detected by qRT-PCR from HCC and corresponding noncancerous tissues was 0.04+/-0.038 and 0.116+/-0.101, respectively. These data demonstrated that KLF6 mRNA level was significantly decreased in HCC, compared with corresponding noncancerous tissues (t =3.683 , P<0.001). The frequency of Hepatoma Cell Lines with KLF6 down-regulation detected by conventional PT-PCR, seems to be consistent with a previous study using real-time PCR assays in tumor samples. KLF6 expression levels were determined by Western blot. Compared to the matched surrounding tissues, a clear decrease of KLF6 protein levels in tumor tissues was observable (t=13.59, P<0.001). Hepatoma cell lines also showed low-level of KLF6 protein (P<0.01) expression. Immunohistochemistry and immunocytochemistry showed a faint diffused staining in the HCC tissues and hepatoma cell lines, and endogenous KLF6 protein was detected mostly in the cytoplasm. KLF6 gene appeared markedly reduced in HCC tissues and hepatoma cell lines. Frequent down-regulation of KLF6 strongly suggested that it is a candidate of tumor suppressor gene for HCC.
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PMID:Loss of expression of Kruppel-like factor 6 in primary hepatocellular carcinoma and hepatoma cell lines. 1755 Jan 40

KLF6 is ubiquitously expressed in human tissues and regulates many pathways such as differentiation, development, cellular proliferation, growth-related signal transduction, and apoptosis. We previously demonstrated that KLF6 expression is altered during liver carcinogenesis. More importantly, KLF6 invalidation results in cell cycle progression inhibition and apoptosis of liver cancer cells. On the other hand, enforced expression of KLF6 variant 2 (SV2) induces cancer cell death by apoptosis. Thus, we and others demonstrated that KLF6 and its splicing variants play a critical role in liver cancer. However, little is known on the mechanisms governing KLF6 expression in HCC. In the present work, we asked whether the 3' untranslated region (3'UTR) of the KLF6 mRNA may be responsible for regulation of KLF6 expression in HCC. We found that KLF6 mRNA stability was altered in liver-derived cell lines as compared to cervical cancer-derived cell lines and human embryonic fibroblasts. Interestingly, KLF6 mRNA was highly unstable in liver cancer-derived cell lines as compared to normal hepatocytes. We next cloned the KLF6 mRNA 3'UTR into luciferase-expressing vectors and found that gene expression and activity were strongly impaired in all liver-derived cell lines tested. In addition, we found that most the KLF6 3'UTR destabilisation activity resides between nt 1,835 and nt 2,615 of the KLF6 gene. Taken together, we provide the first steps towards better understanding of the regulation of KLF6 expression in HCC. Further work is needed to identify the factors that bind to KLF6 3'UTR to regulate its expression in liver cancer-derived cell lines.
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PMID:The Role of the 3' Untranslated Region in the Post-Transcriptional Regulation of KLF6 Gene Expression in Hepatocellular Carcinoma. 2437 51