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Ribonucleotide reductase small subunit p53R2 promotes oral cancer invasion via the E-cadherin/beta-catenin pathway.

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タイトル: Ribonucleotide reductase small subunit p53R2 promotes oral cancer invasion via the E-cadherin/beta-catenin pathway.
著者: Yanamoto, Souichi / Kawasaki, Goro / Yamada, Shin-ichi / Yoshitomi, Izumi / Yoshida, Hajime / Mizuno, Akio
発行日: 2009年 6月
出版者: Elsevier Ltd
引用: Oral Oncology, 45(6), pp.521-525; 2009
抄録: The p53-inducible p53R2 gene has been isolated and shown to play a crucial role in DNA repair and synthesis after DNA damage. Moreover, the expression and activity of p53R2 has been reported to be associated with the anticancer agent resistance of human cancer cells. Previously, we reported that the presence of p53R2 expression was a predictive factor for regional lymph node metastasis in oral squamous cell carcinoma; however, the mechanism of cancer metastasis by p53R2 expression is still unclear. In the present study, we analyzed the correlation of p53R2 expression with cancer invasion in vitro. Three human oral cancer cell lines (SAS, HSC-3 and Ca9-22) were cultured, and the invasive potential of these cancer cells was evaluated using Matrigel invasion assay. To investigate the effect of p53R2 on cancer invasion, the down-regulation of p53R2 was examined by small interfering RNA (siRNA). Moreover, we examined the intracellular localization of cell adhesion molecules (E-cadherin and beta-catenin) in subcellular extractions of cancer cells by immunoblotting. The proteolytic activity of matrix metalloproteinases (MMPs) was assessed by gelatin zymography. Down-regulation of p53R2 significantly enhanced the invasion potential (p<0.01), and enhanced nuclear translocation of beta-catenin with loss of total cellular E-cadherin expression in p53 mutant cancer cells, but not in p53 wild-type cancer cells. These changes in the invasion index by p53R2 siRNA transfection were not accompanied by alterations in MMP activity and expression. These results suggested that the expression of p53R2 could be associated with the invasion of cancer cells, and indicated that p53R2 might promote cancer invasion via the E-cadherin/beta-catenin pathway without the alteration of MMP activity.
キーワード: p53R2 / Invasion / E-cadherin / β-catenin / Small interfering RNA
URI: http://hdl.handle.net/10069/20064
ISSN: 13688375
DOI: 10.1016/j.oraloncology.2008.07.005
PubMed ID: 18804405
権利: Copyright © 2008 Elsevier Ltd All rights reserved.
資料タイプ: Journal Article
原稿種類: author
出現コレクション:130 学術雑誌論文

引用URI : http://hdl.handle.net/10069/20064



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