Stat3 up-regulates expression of nicotinamide N-methyltransferase in human cancer cells
- 6 October 2007
- journal article
- Published by Springer Nature in Zeitschrift für Krebsforschung und Klinische Onkologie
- Vol. 134 (5) , 551-559
- https://doi.org/10.1007/s00432-007-0318-6
Abstract
To discover new molecular targets for cancer therapy and diagnosis, we surveyed signal transducers and activators of transcription 3 (Stat3)-regulated genes, because constitutive activation of Stat3 is associated with a wide variety of human malignancies. We investigated the Stat3-regulated genes in 293 cells with cDNA microarray analysis and found that Nicotinamide N-methyltransferase (NNMT) was induced on stimulation of the cells with leukemia inhibitory factor. We examined the expression of NNMT in several types of cancer cells by real-time quantitative RT-PCR. To examine the role of Stat3, Hep-G2 hepatocellular carcinoma cells were transfected with NNMT promoter-luciferase reporter construct together with conditionally active Stat3 (Stat3ER) or dominant-negative Stat3 expression vector and NNMT promoter activity was determined. The expression of NNMT and activated Stat3 in 88 colon cancer tissues and 17 normal colon tissues was examined with immunohistochemical analysis. In Hep-G2 cells and SW480 colon cancer cells, NNMT expression increased on stimulation of the cells with interleukin 6. NNMT promoter activity in Hep-G2 cells was dependent on the activation of Stat3. MDA-MB-468 breast cancer cells and HT29 colon cancer cells expressed constitutively a high level of NNMT. Treatment of these cells with Stat3 siRNA or curcumin, which inhibited Stat3 phosphorylation, resulted in reduction of the NNMT level. We found a correlation between the expression of NNMT and activated Stat3 (P < 0.001) in the colon cancer tissues. NNMT is a novel Stat3-regulated gene. Its expression is enhanced with the activation of Stat3 in colon cancer tissues. NNMT may be a potential candidate for a tumor marker of various kinds of cancers.Keywords
This publication has 48 references indexed in Scilit:
- Constitutively Activated Stat3 Induces Tumorigenesis and Enhances Cell Motility of Prostate Epithelial Cells through Integrin β6Molecular and Cellular Biology, 2007
- Overexpression of nicotinamide N-methyltransferase in gastric cancer tissues and its potential post-translational modificationExperimental & Molecular Medicine, 2006
- Constitutive Activation of JAK3/STAT3 in Colon Carcinoma Tumors and Cell LinesThe American Journal of Pathology, 2005
- Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma; correlation with clinicopathological factorsJournal of Clinical Pathology, 2005
- The STATs of cancer — new molecular targets come of ageNature Reviews Cancer, 2004
- Interleukin-6–dependent gene expression profiles in multiple myeloma INA-6 cells reveal a Bcl-2 family–independent survival pathway closely associated with Stat3 activationBlood, 2004
- STAT proteins: novel molecular targets for cancer drug discoveryOncogene, 2000
- Human nicotinamide N-methyltransferase pharmacogeneticsPharmacogenetics, 1999
- Human NicotinamideN-Methyltransferase Gene: Molecular Cloning, Structural Characterization and Chromosomal LocalizationGenomics, 1995
- Stat3: a STAT Family Member Activated by Tyrosine Phosphorylation in Response to Epidermal Growth Factor and Interleukin-6Science, 1994