New candidate tumor-suppressor gene KLF6 and its splice variant KLF6 SV2 counterbalancing expression in primary hepatocarcinoma

Hepatogastroenterology. 2012 Mar-Apr;59(114):473-6. doi: 10.5754/hge11283.

Abstract

Background/aims: This study aimed to detect the expression of newly discovered zinc finger transcriptional factor KLF6 and its splice variant KLF6 SV2 in primary hepatocarcinoma (PHC) tissues and hepatoma cell strains, and to evaluate their clinicopathologic relationship with PHC.

Methodology: Wild-type KLF6 and KLF6 SV2 mRNA expression was determined by RTPCR in 27 cases of PHC tissues and cell strains of HepG2, SMMC7721 and LO2. Western blotting and immunohistochemical staining were adopted to detect KLF6 protein expression. Positive area ratio of wild-type KLF6 protein expression and its relationship with clinicopathological parameters of PHC was analyzed.

Results: Wild-type KLF6 expression in PHC tissues was lower than that in paracancerous tissues. In contrast, KLF6 SV2 mRNA expression was higher in PHC tissues and hepatoma cell strains (p<0.05). Positive area ratio of wild-type KLF6 protein expression was positively correlated with cellular differentiation degree of PHC (p<0.01), but negatively correlated not only with liver cirrhosis, tumor size and extrahepatic metastases (p<0.01), but also with portal vein thrombus and the number of lymph nodes with metastasis (p<0.05).

Conclusions: Wild-type KLF6 deletion and inactivation was involved in the growth, cell differentiation and other physiological processes of PHC. The upregulation of KLF6 splice variant might counterbalance the wildtype KLF6 and contribute to the occurrence and development of PHC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / secondary
  • Cell Differentiation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Hep G2 Cells
  • Humans
  • Immunohistochemistry
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Protein Isoforms
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Burden
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Venous Thrombosis / metabolism
  • Venous Thrombosis / pathology

Substances

  • KLF6 protein, human
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins