Telomerase regulation and progressive telomere shortening of rat hepatic stem-like epithelial cells during 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.
Oh
Bong-Kyeong
BK
Department of Pathology, Center for Chronic Metabolic Disease Research and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
Lee
Chan-Hee
CH
Park
Chanil
C
Park
Young Nyun
YN
D000818:Animals; D020134:Catalytic Domain / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D016922:Cellular Senescence / Q000235:genetics*; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology*; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D004268:DNA-Binding Proteins; D012313:RNA; D019098:Telomerase