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Telomerase regulation and progressive telomere shortening of rat hepatic stem-like epithelial cells during in vitro aging

 Bong-Kyeong Oh  ;  Chan-Hee Lee  ;  Young Nyun Park  ;  Chanil Park 
 EXPERIMENTAL CELL RESEARCH, Vol.298(2) : 445-454, 2004 
Journal Title
Issue Date
Animals ; Catalytic Domain/genetics ; Cell Differentiation/genetics ; Cell Division/genetics ; Cell Line ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cellular Senescence/genetics* ; DNA-Binding Proteins ; Epithelial Cells/cytology ; Epithelial Cells/enzymology* ; Gene Expression Regulation, Neoplastic/genetics ; Hepatocytes/cytology ; Hepatocytes/enzymology* ; Liver/cytology ; Liver/enzymology ; Liver/growth & development ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; RNA/genetics ; RNA/metabolism ; Rats ; Stem Cells/cytology ; Stem Cells/enzymology* ; Telomerase/genetics ; Telomerase/metabolism* ; Telomere/metabolism* ; Up-Regulation/genetics
Rat hepatic stem-like epithelial cell ; Telomerase ; Telomere ; Transformation ; In vitro aging
Rat hepatic stem-like epithelial cells, LE/2, LE/6, and WB-F344, share some phenotypic properties with oval cells, observed in the early stages of hepatocarcinogenesis. Here, we describe regulations of telomerase and telomere length during in vitro aging of LEs and WB-F344. These cells displayed no apparent aging phenotypes for over 140 passages. Telomerase activity and telomere length of these cells progressively decreased with the passages, and at the late passages, telomere shortening appeared to be reduced as telomerase activity increased. Regulation of TERT and TR, key components of telomerase, was similar to that of the telomerase activity. LEs possessed weak telomerase activity with a slow rate of proliferation compared to WB-F344, and were not tumorigenic, whereas WB-F344 was transformed in vitro from intermediate passage. In conclusion, LEs and WB-F344 have different biochemical properties, and telomerase activation and short telomeres are unlikely necessary for the transformation of WB-F344. TERT and TR seem to be the regulators of the telomerase activity. The relationship between telomere length and telomerase activity suggests that telomerase contributes to the regulation of telomere length in these cells. Our findings provide a better understanding of mechanisms in neoplastic transformation of rat hepatic stem-like epithelial cells.
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5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
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)
Oh, Bong Kyeong(오봉경)
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