Interferon-alpha upregulates thymidine phosphorylase expression via JAK-STAT transcriptional activation and mRNA stabilization in human hepatocellular carcinoma SMMC-7721 cells.
- Author:
Yong-sheng XIAO
1
;
Jian ZHOU
;
Jia FAN
;
Qi-man SUN
;
Yan ZHAO
;
Rui-xia SUN
;
Yin-kun LIU
;
Zhao-you TANG
Author Information
- Publication Type:Journal Article
- MeSH: Carcinoma, Hepatocellular; enzymology; pathology; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme Inhibitors; pharmacology; Gene Expression Regulation, Neoplastic; Humans; Interferon-alpha; administration & dosage; pharmacology; Janus Kinases; metabolism; Liver Neoplasms; enzymology; pathology; RNA, Messenger; metabolism; STAT1 Transcription Factor; metabolism; Thymidine Phosphorylase; biosynthesis; genetics; Transcriptional Activation; drug effects; Tyrphostins; pharmacology
- From: Chinese Journal of Oncology 2008;30(6):444-447
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo examine how the thymidine phosphorylase (TP) gene expression is upregulated by interferon-alpha (IFN-alpha) in human hepatocellular carcinoma SMMC-7721 cells.
METHODSTP mRNA levels were determined by RT-PCR. Whether the JAK-STAT cascade mediates IFN-alpha-induced TP mRNA expression was studied by pretreatment with Janus Kinase (JAK) inhibitor, AG-490. Effects of IFN-alpha on TP mRNA stability were detected with additional actinomycin D.
RESULTSThe expression of TP mRNA was induced by IFN-alpha in a dose- and time-dependent manner in SMMC-7721 (human hepatocellular carcinoma) cells. TP mRNA levels rose at 8 h, reached the peak value at 12 h, and remained at a high level up to 72 h in SMMC-7721 cells treated with IFN-alpha 10000 U/ml. IFN-alpha at a dose of 5000 or 10000 U/ml up-regulated TP expression about 3 fold compared with that of non-treated cells (P < 0.05). Induction of TP mRNA expression by IFN-alpha was significantly inhibited in SMMC-7721 cells by pretreatment with AG-490, in comparison with that treated with IFN-alpha alone. Pretreatment of SMMC-7721 cells with IFN-alpha 10000 U/ml for 24 h caused a substantial stabilization of TP mRNA, with a half-live of 35.8 h, compared with 8.5 hr in the control SMMC-7721 cells.
CONCLUSIONIFN-alpha at certain doses upregulates TP mRNA expression via both JAK-STAT transcriptional activation and post-transcriptional mRNA stabilization in human hepatocellular carcinoma SMMC-7721 cells.
