RRM2 induces NF-kappaB-dependent MMP-9 activation and enhances cellular invasiveness.
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.
Duxbury
Mark S
MS
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Whang
Edward E
EE
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012262:Ribonucleoside Diphosphate Reductase / Q000378:metabolism*
D016328:NF-kappa B; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase; D020780:Matrix Metalloproteinase 9