1. RNAi-mediated down-regulation of alpha-actinin-4 decreases invasion potential in oral squamous cell carcinoma.
- Author
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Yamada S, Yanamoto S, Yoshida H, Yoshitomi I, Kawasaki G, Mizuno A, and Nemoto TK
- Subjects
- Actinin analysis, Blotting, Western, Carcinoma, Squamous Cell pathology, Cell Line, Tumor, Cell Nucleus ultrastructure, Cytoplasm ultrastructure, Diffusion Chambers, Culture, Female, Gene Knockdown Techniques, Humans, Immunohistochemistry, Keratinocytes cytology, Male, Middle Aged, Mouth Mucosa cytology, Mouth Neoplasms pathology, Neoplasm Invasiveness genetics, Neoplasm Staging, Phenotype, RNA, Small Interfering therapeutic use, Reverse Transcriptase Polymerase Chain Reaction, Actinin genetics, Carcinoma, Squamous Cell genetics, Down-Regulation physiology, Gene Expression Regulation, Neoplastic genetics, Mouth Neoplasms genetics, RNA Interference physiology
- Abstract
alpha-actinin-4, originally identified as an actin-binding protein associated with cell motility, invasion, and metastasis of cancer cells, appears to be overexpressed in various human epithelial carcinomas, including colorectal, breast, esophageal, ovarian, and non-small cell lung carcinomas. The authors evaluated whether alpha-actinin-4 might be appropriate as a molecular target for cancer gene therapy. In 64 primary oral squamous cell carcinomas (OSCCs) and 10 normal oral mucosal specimens, and in seven human OSCC cell lines, alpha-actinin-4 expression was evaluated immunologically and correlations with clinicopathologic factors were examined. Overexpression of alpha-actinin-4 was detected in 38 of 64 oral squamous cell carcinomas (70%); significantly more frequently than in normal oral mucosa. The expression of alpha-actinin-4 was significantly associated with invasion potential defined by the Matrigel invasion assay. Cancer cell lines with higher alpha-actinin-4 expression had greater invasive potential. An RNAi-mediated decrease in alpha-actinin-4 expression reduced the invasion potential. These results indicated that the overexpression of alpha-actinin-4 was associated with an aggressive phenotype of OSCC. The study indicated that alpha-actinin-4 could be a potential molecular target for gene therapy by RNAi targeting for OSCC., (Copyright 2009 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2010
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