NF-kappaB p65 modulates the telomerase reverse transcriptase in the HepG₂ hepatoma cell line

• Published in: European journal of pharmacology 2011-12, Vol.672 (1-3), p.113-120
• Main Authors: Zuo, Qing-Ping, Liu, Shi-Kun, Li, Zuo-Jun, Li, Bing, Zhou, Yu-Lu, Guo, Ren, Huang, Li-Hua
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; carcinogenesis; Carcinoma, Hepatocellular - pathology; Cell Survival - drug effects; Dexamethasone; Dexamethasone - pharmacology; Dose-Response Relationship, Drug; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; gene expression regulation; genes; Hep G2 Cells; Hepatocellular carcinoma; Hepatoma; Humans; Inflammation; Leupeptins - pharmacology; Lipopolysaccharides; Lipopolysaccharides - pharmacology; liver; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; messenger RNA; Molecular Targeted Therapy; NF- Kappa B protein; Nuclear transport; Pharmacology. Drug treatments; Proteasome Endopeptidase Complex; Proteasome Inhibitors; proteasomes; Protein Biosynthesis - drug effects; protein synthesis; RNA, Messenger - genetics; RNA, Messenger - metabolism; telomerase; Telomerase - biosynthesis; Telomerase - genetics; Telomerase - metabolism; telomerase reverse transcriptase; Time Factors; TLR4 protein; Toll-like receptors; transcription (genetics); transcription factor NF-kappa B; Transcription Factor RelA - metabolism; Transcription factors; Transcription, Genetic - drug effects; Tumorigenesis; Tumors; Up-Regulation - drug effects
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2011.09.187

Nuclear factor-kappa B (NF-kappaB) regulates the expression of various genes, several genes involved in inflammation and tumorigenesis, including those of the liver. A role for NF-kappaB has been implicated in the pathogenesis of hepatocellular carcinoma. This transcription factor can regulate hTERT gene transcription. Expression of hTERT was found to be at high levels in hepatocellular carcinoma. However, positive effects of NF-kappaB on hTERT protein synthesis in HepG₂ cells are unknown. In this study, we show that LPS (specific binding to TLR4 to activate NF-kappaB) was positive for NF-kappaB p65 mRNA expression and activation, and also up-regulated hTERT mRNA and protein expressions at 36h in a dose-dependent manner. In contrast, MG-132 (blocking the activity of 26S proteasome and thereby preventing nuclear translocation of NF-kappaB) significantly inhibited activation of NF-kappaB and mRNA expression. And also reduced the expression of hTERT at both mRNA and protein levels at 36h in a dose-dependent manner. Furthermore, dexamethasone inhibited LPS-induced activation of NF-kappaB and expression of the hTERT in HepG₂ cells. These findings suggest that NF-kappaB may modulate hTERT mRNA level, importantly, in protein level in HepG₂ cells and dexamethasone inhibits LPS-induced hTERT via blocking NF-kappaB.