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Stat3 up-regulates expression of nicotinamide N-methyltransferase in human cancer cells

Mikio Tomida1, Hideki Ohtake, Takashi Yokota

  • 1Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina, Saitama 362-0806, Japan. tomida@cancer-c.pref.saitama.jp.

Journal of Cancer Research and Clinical Oncology
|October 9, 2007
PubMed
Abstract

Insights

Nicotinamide N-methyltransferase (NNMT) is a novel gene regulated by signal transducers and activators of transcription 3 (Stat3). NNMT expression correlates with Stat3 activation in colon cancer, suggesting its potential as a tumor marker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Constitutive activation of signal transducers and activators of transcription 3 (Stat3) is implicated in numerous human cancers.
  • Identifying Stat3-regulated genes is crucial for discovering novel cancer therapeutic and diagnostic targets.

Purpose of the Study:

  • To identify novel molecular targets for cancer therapy and diagnosis by surveying Stat3-regulated genes.
  • To investigate the role of Nicotinamide N-methyltransferase (NNMT) as a potential Stat3-regulated gene in various cancers.

Main Methods:

  • Utilized cDNA microarray analysis to identify Stat3-induced genes in 293 cells.
  • Examined NNMT expression in cancer cell lines using real-time quantitative RT-PCR.
  • Assessed NNMT promoter activity in response to Stat3 activation in Hep-G2 cells.
  • Performed immunohistochemical analysis of NNMT and activated Stat3 in colon cancer tissues.

Main Results:

  • Nicotinamide N-methyltransferase (NNMT) was identified as a Stat3-induced gene.
  • NNMT expression and promoter activity were found to be dependent on Stat3 activation in cancer cells.
  • A significant correlation between NNMT expression and activated Stat3 was observed in colon cancer tissues.
  • NNMT levels decreased upon inhibition of Stat3 phosphorylation.

Conclusions:

  • Nicotinamide N-methyltransferase (NNMT) is a newly identified Stat3-regulated gene.
  • Elevated NNMT expression is associated with Stat3 activation in colon cancer.
  • NNMT represents a potential candidate biomarker for various cancer types.

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