Literature DB >> 19015875

Frequent inactivation of RUNX3 by promoter hypermethylation and protein mislocalization in oral squamous cell carcinomas.

Feng Gao1, Canhua Huang, Mei Lin, Zhi Wang, Jun Shen, Haiyuan Zhang, Lu Jiang, Qianming Chen.   

Abstract

PURPOSE: RUNX3 is a functionally important component in transforming growth factor-beta (TGF-beta) mediated signaling pathway. Epigenetic silencing expression of RUNX3, as well as aberrant cytoplasmic retention of RUNX3 protein are causally involved in gastric carcinogenesis. Here, we examined the expression of RUNX3 gene and protein in oral squamous cell carcinomas (OSCCs) and analyzed the methylation status of RUNX3 promoter region.
METHODS: About 10 normal oral mucosa and 30 OSCCs were collected to examine RUNX3 expression by RT-PCR analysis and immunohistochemistry assay using anti-RUNX3 monoclonal antibody R3-6E9. Methylation-specific PCR was carried out on the same specimens to analyze the methylation status of RUNX3 promoter. In addition, the stored paraffin-embedded specimens, including 40 oral leucoplakia (OLK) and 120 OSCCs, were examined by immunohistochemistry assay.
RESULTS: RUNX3 gene and protein were underexpressed in OSCCs due to promoter hypermethylation. Protein mislocalization occurred frequently. Both downregulation of RUNX3 protein expression (P = 0.001) and protein mislocalization (P = 0.001) were correlated with the differentiation grades in OSCCs.
CONCLUSIONS: RUNX3 plays an important role in oral carcinogenesis. It may be a useful diagnostic marker and a potential therapeutic target for OSCC.

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Year:  2008        PMID: 19015875     DOI: 10.1007/s00432-008-0508-x

Source DB:  PubMed          Journal:  J Cancer Res Clin Oncol        ISSN: 0171-5216            Impact factor:   4.553


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