Exp Mol Med.  2006 Jun;38(3):247-255.

Genetic and expression analysis of the KCNRG gene in hepatocellular carcinomas

• Cho YG
• Kim CJ
• Song JH
• Rhie DJ
• Park YK
• Kim SY
• Nam SW
• Yoo NJ
• Lee JY
• Park WS

Abstract

The potassium channels are ubiquitous multisubunit membrane proteins, and potassium-dependent alterations in the membrane potential play an important role in the proliferation of many types of cells. This study analyzed the mutation, allelic loss and expression patterns of the KCNRG gene in 77 HCCs in order to determine if the KCNRG gene, which encodes the potassium channel regulating protein, is involved in the tumorigenesis of hepatocellular carcinoma (HCC). One KCNRG missense mutation, CGT->CAT (Arg->His) was found at codon 92 within the T1 domain. Hep3B hepatoma cells were transfected with the wild- or mutant-KCNRG to determine the effect of this mutation in KCNRG. Interestingly, the suppressive cell growth activity of the mutant-type KCNRG was significantly lower than that of the wild-type KCNRG. In addition, allelic loss was detected in 17 out of 64 (26.5%) informative HCC cases, and all were hepatitis B virus (HBV)-positive. Moreover, the allelic loss was closely related to an intrahepatic metastasis (P=0.0247), higher grade (P=0.0078) and clinical stage (P=0.0071). Expression analysis revealed 22 tumor tissues to have a loss of expression of the KCNRG transcript. These results suggest that genetic alterations and the expression of KCNRG might play an important role in the development and/or progression of a subset of HCCs.

Keyword

carcinoma, hepatocellular; KCNRG protein, human; loss of heterozygosity; mutation, missense; potassium channels

MeSH Terms

Transfection
Reverse Transcriptase Polymerase Chain Reaction
Potassium Channels/*genetics/metabolism
Polymorphism, Single-Stranded Conformational
Mutation/genetics
Middle Aged
Membrane Potentials/genetics/physiology
Male
Loss of Heterozygosity/genetics
Liver Neoplasms/*genetics/metabolism/pathology
Humans
Gene Expression Regulation, Neoplastic/genetics
Female
DNA Mutational Analysis
Cell Proliferation
Cell Line, Tumor
Carcinoma, Hepatocellular/*genetics/metabolism/pathology
Blotting, Western
Aged, 80 and over
Aged
Adult