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Up-Regulation of Telomere-Binding Proteins, TRF1, TRF2, and TIN2 Is Related to Telomere Shortening during Human Multistep Hepatocarcinogenesis

Authors
 Bong-Kyeong Oh  ;  Young-Joo Kim  ;  Chanil Park  ;  Young Nyun Park 
Citation
 AMERICAN JOURNAL OF PATHOLOGY, Vol.166(1) : 73-80, 2005 
Journal Title
 AMERICAN JOURNAL OF PATHOLOGY 
ISSN
 0002-9440 
Issue Date
2005
MeSH
Carcinoma, Hepatocellular/genetics* ; Carcinoma, Hepatocellular/pathology ; DNA Primers ; DNA, Complementary/genetics ; Gene Expression Regulation* ; Humans ; Immunohistochemistry ; Liver Neoplasms/genetics* ; Liver Neoplasms/pathology ; Reverse Transcriptase Polymerase Chain Reaction ; Telomere/genetics* ; Telomere-Binding Proteins/genetics* ; Telomeric Repeat Binding Protein 1/genetics* ; Telomeric Repeat Binding Protein 2/genetics*
Keywords
15632001
Abstract
The telomeric repeat-binding factor 1 (TRF1), TRF2, and the TRF1-interacting nuclear protein 2 (TIN2) are involved in telomere maintenance. We describe the regulation of expression of these genes along with their relationship to telomere length in hepatocarcinogenesis. The transcriptional expression of these genes, TRF1 protein, and telomere length was examined in 9 normal livers, 14 chronic hepatitis, 24 liver cirrhosis, 5 large regenerative nodules, 14 low-grade dysplastic nodules (DNs), 7 high-grade DNs, 10 DNs with hepatocellular carcinoma (HCC) foci, and 31 HCCs. The expression of TRF1, TRF2, TIN2 mRNA, and TRF1 protein was gradually increased according to the progression of hepatocarcinogenesis with a marked increase in high-grade DNs and DNs with HCC foci and a further increase in HCCs. There was a gradual shortening of telomere during hepatocarcinogenesis with a significant reduction in length in DNs. Most nodular lesions (52 of 67) had shorter telomeres than their adjacent chronic hepatitis or liver cirrhosis, and the telomere lengths were inversely correlated with the mRNA level of these genes (P </= 0.001). This was more evident in DNs and DNs with HCC foci. In conclusion, TRF1, TRF2, and TIN2 might be involved in multistep hepatocarcinogenesis by playing crucial roles in telomere shortening.
Files in This Item:
T200500299.pdf Download
DOI
10.1016/S0002-9440(10)62233-X
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Park, Chan Il(박찬일)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/147545
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