Interferon-alpha upregulates thymidine phosphorylase expression via JAK-STAT transcriptional activation and mRNA stabilization in human hepatocellular carcinoma SMMC-7721 cells / 中华肿瘤杂志
Chinese Journal of Oncology
;
(12): 444-447, 2008.
Article
in Chinese
| WPRIM
| ID: wpr-357403
ABSTRACT
<p><b>OBJECTIVE</b>To examine how the thymidine phosphorylase (TP) gene expression is upregulated by interferon-alpha (IFN-alpha) in human hepatocellular carcinoma SMMC-7721 cells.</p><p><b>METHODS</b>TP 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>IFN-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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Thymidine Phosphorylase
/
RNA, Messenger
/
Gene Expression Regulation, Neoplastic
/
Transcriptional Activation
/
Interferon-alpha
/
Carcinoma, Hepatocellular
/
Tyrphostins
/
Cell Line, Tumor
Limits:
Humans
Language:
Chinese
Journal:
Chinese Journal of Oncology
Year:
2008
Type:
Article
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