RRC ID 38305
著者 Furuta H, Kondo Y, Nakahata S, Hamasaki M, Sakoda S, Morishita K.
タイトル NDRG2 is a candidate tumor-suppressor for oral squamous-cell carcinoma.
ジャーナル Biochem Biophys Res Commun
Abstract Oral cancer is one of the most common cancers worldwide, and squamous-cell carcinoma (OSCC) is the most common phenotype of oral cancer. Although patients with OSCC have poor survival rates and a high incidence of metastasis, the molecular mechanisms of OSCC development have not yet been elucidated. This study investigated whether N-myc downstream-regulated gene 2 (NDRG2) contributes to the carcinogenesis of OSCC, as NDRG2 is reported to be a candidate tumor-suppressor gene in a wide variety of cancers. The down-regulation of NDRG2 mRNA, which was dependent on promoter methylation, was seen in the majority of OSCC cases and in several cases of precancerous leukoplakia with dysplasia. Induction of NDRG2 expression in an HSC-3/OSCC cell line significantly inhibited cell proliferation and decreased colony formation ability on soft agar. The majority of OSCC cell lines showed an activation of PI3K/Akt signaling, and enforced expression of NDRG2 in HSC-3 cells decreased the level of phosphorylated Akt at Serine 473 (p-Akt). Immunohistochemical p-Akt staining was detected in 56.5% of the OSCC tumors, and 80.4% of the tumors were negative for NDRG2 staining. Moreover, positive p-Akt staining was inversely correlated with decreased NDRG2 expression in OSCC tumors with moderate to poor differentiation (p<0.005). Therefore, NDRG2 is a candidate tumor-suppressor gene for OSCC development and probably contributes to the tumorigenesis of OSCC partly via the modulation of Akt signaling.
巻・号 391(4)
ページ 1785-91
公開日 2010-1-22
DOI 10.1016/j.bbrc.2009.12.156
PII S0006-291X(09)02554-6
PMID 20045673
MeSH Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / metabolism Cell Line, Tumor DNA Methylation Down-Regulation Gene Expression Regulation, Neoplastic* Humans Mouth Neoplasms / genetics* Mouth Neoplasms / metabolism Promoter Regions, Genetic Proto-Oncogene Proteins c-akt / metabolism Tumor Suppressor Proteins / genetics*
IF 2.985
引用数 36
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞