Duxbury Mark S, Whang Edward E
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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.
核糖核苷酸还原酶是一种二聚体酶，催化核糖核苷酸5'-二磷酸转化为其2'-脱氧核苷酸形式，这是DNA合成所需的2'-脱氧核糖核苷5'-三磷酸生产中的限速步骤。核糖核苷酸还原酶M2亚基（RRM2）是一系列人类癌症中恶性细胞行为的决定因素。我们研究了RRM2过表达对胰腺腺癌细胞侵袭性和核因子-κB（NF-κB）转录因子活性的影响。RRM2过表达以NF-κB依赖的方式增加胰腺腺癌细胞侵袭性和MMP-9表达。RNA干扰（RNAi）介导的RRM2表达沉默减弱细胞侵袭性和NF-κB活性。NF-κB是RRM2过表达诱导的侵袭性表型变化的关键介质。
