Nuclear translocation of telomerase reverse transcriptase: a critical process in chemical induced hepatocellular carcinogenesis.
Telomerase, a ribonuclearprotein complex, functions not only in cancer development but also in apoptosis, and senescence. As a catalytic subunit of telomerase, telomerase reverse transcriptase (TERT) has been confirmed to regulate telomerase activity in a rate-limiting manner. Although a lot of work has been done, the dynamic state of TERT protein and the relationship with telomerase have not been delineated systematically in cancer development. The purpose of this study was to do such an exploration. To investigate the role of TERT in the in vivo carcinogenesis, we performed immunofluorescence and Western blot analysis, respectively, to detect the alteration of TERT status as well as telomeric repeat amplification protocol (TRAP) assay to detect telomerase activity in diethyl nitrosoamine (DENA) induced rat hepatocellular carcinoma (HCC). The course of cancer development was divided into three main stages, which were inflammation ( <12 weeks), hepatocirrhosis (15 weeks), and hepatocarcinoma (18-21 weeks). In normal liver and its early inflammatory stage, concomitant with a weak positive TERT signal, which was detected exclusively in the cytoplasm, telomerase activity was very low at this stage. However, in late hepatocirrhosis and particularly cancer stage, high levels of TERT expression (P = 0.044 and P = 0.001, respectively) and telomerase activity (P = 0.02 and P = 0.01, respectively) were observed following TERT nuclear translocation. Our data suggest that TERT protein might regulate telomerase activity. TERT translocation from cytoplasm to the nucleus might be a turning point in cancer development. Therefore, TERT translocation might be more useful than TERT expression level and telomerase activity in predicting the progression of HCC.
Chen
Y
Y
School of Life Science and Technology, Henan Institute of Science and Technology, Xinxiang City, China.
Kong
Q
Q
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004052:Diethylnitrosamine; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D019098:Telomerase / Q000378:metabolism*
D004052:Diethylnitrosamine; D019098:Telomerase