Genetic and expression analysis of the KCNRG gene in hepatocellular carcinomas.
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.
Cho
Yong Gu
YG
Department of Pathology, College of Medicine, The Catholic University of Korea.
Kim
Chang Jae
CJ
Song
Jae Hwi
JH
Rhie
Duck Joo
DJ
Park
Yong Kyu
YK
Kim
Su Young
SY
Nam
Suk Woo
SW
Yoo
Nam Jin
NJ
Lee
Jung Young
JY
Park
Won Sang
WS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C473317:KCNRG protein, human; D015221:Potassium Channels