RRM2 induces NF-{kappa}B-dependent MMP-9 activation and enhances cellular invasiveness

Journal Article · Fri Mar 02 00:00:00 EST 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.12.177· OSTI ID:20979817

Duxbury, Mark S ^[1]; Whang, Edward E ^[1]

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1. Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (United States)

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-{kappa}B (NF-{kappa}B) transcription factor activity. RRM2 overexpression increases pancreatic adenocarcinoma cellular invasiveness and MMP-9 expression in a NF-{kappa}B-dependent manner. RNA interference (RNAi)-mediated silencing of RRM2 expression attenuates cellular invasiveness and NF-{kappa}B activity. NF-{kappa}B is a key mediator of the invasive phenotypic changes induced by RRM2 overexpression.

• OSTI ID: 20979817
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 354, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.12.177; PII: S0006-291X(06)02856-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOSYNTHESIS
CARCINOMAS
DNA
ENZYMES
PANCREAS
RNA
TRANSCRIPTION FACTORS