Genetic and expression analysis of the KCNRG gene in hepatocellular carcinomas.
- Author:
Yong Gu CHO
1
;
Chang Jae KIM
;
Jae Hwi SONG
;
Duck Joo RHIE
;
Yong Kyu PARK
;
Su Young KIM
;
Suk Woo NAM
;
Nam Jin YOO
;
Jung Young LEE
;
Won Sang PARK
Author Information
1. Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea. wonsang@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
carcinoma, hepatocellular;
KCNRG protein, human;
loss of heterozygosity;
mutation, missense;
potassium channels
- MeSH:
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
- From:Experimental & Molecular Medicine
2006;38(3):247-255
- CountryRepublic of Korea
- Language:English
-
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.
