RRM2 induces NF-kappaB-dependent MMP-9 activation and enhances cellular invasiveness

Biochem Biophys Res Commun. 2007 Mar 2;354(1):190-6. doi: 10.1016/j.bbrc.2006.12.177. Epub 2006 Dec 29.


Ribonucleotide reductase is a dimeric enzyme that catalyzes conversion of ribonucleotide 5'-diphosphates to their 2'-deoxynucleotide forms, a rate-limiting step in the production of 2'-deoxyribonucleoside 5'-triphosphates required for DNA synthesis. The ribonucleotide reductase M2 subunit (RRM2) is a determinant of malignant cellular behavior in a range of human cancers. We examined the effect of RRM2 overexpression on pancreatic adenocarcinoma cellular invasiveness and nuclear factor-kappaB (NF-kappaB) transcription factor activity. RRM2 overexpression increases pancreatic adenocarcinoma cellular invasiveness and MMP-9 expression in a NF-kappaB-dependent manner. RNA interference (RNAi)-mediated silencing of RRM2 expression attenuates cellular invasiveness and NF-kappaB activity. NF-kappaB is a key mediator of the invasive phenotypic changes induced by RRM2 overexpression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Enzyme Activation
  • Humans
  • Matrix Metalloproteinase 9 / metabolism*
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • Ribonucleoside Diphosphate Reductase / metabolism*


  • NF-kappa B
  • ribonucleotide reductase M2
  • Ribonucleoside Diphosphate Reductase
  • Matrix Metalloproteinase 9