NF-kappaB p65 modulates the telomerase reverse transcriptase in the HepG₂ hepatoma cell line.
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 HepG(2) 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 HepG(2) cells. These findings suggest that NF-kappaB may modulate hTERT mRNA level, importantly, in protein level in HepG(2) cells and dexamethasone inhibits LPS-induced hTERT via blocking NF-kappaB.
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Qing-Ping
QP
Zuo
Shi-Kun
SK
Liu
Zuo-Jun
ZJ
Li
Bing
B
Li
Yu-Lu
YL
Zhou
Ren
R
Guo
Li-Hua
LH
Huang
D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D007976:Leupeptins; D008070:Lipopolysaccharides; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D003907:Dexamethasone; D019098:Telomerase; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde