A novel Myc-target gene, mimitin, that is involved in cell proliferation of esophageal squamous cell carcinoma

被引:29
作者
Tsuneoka, M [1 ]
Teye, K
Arima, N
Soejima, M
Otera, H
Ohashi, K
Koga, Y
Fujita, H
Shirouzu, K
Kimura, H
Koda, Y
机构
[1] Kurume Univ, Sch Med, Div Human Genet, Dept Forens Med, Kurume, Fukuoka 8300011, Japan
[2] Kurume Univ, Sch Med, Dept Pathol, Kurume, Fukuoka 8300011, Japan
[3] Kurume Univ, Sch Med, Dept Pediat & Child Hlth, Kurume, Fukuoka 8300011, Japan
[4] Kurume Univ, Sch Med, Dept Surg, Kurume, Fukuoka 8300011, Japan
[5] Kyushu Univ, Grad Sch Med Sci, Dept Mol Biol, Fukuoka 8128582, Japan
[6] Chiba Univ, Grad Sch Sci & Technol, Chiba 2638522, Japan
[7] Chiba Inst Sci, Choshi 2880025, Japan
关键词
D O I
10.1074/jbc.M501231200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Myc is a ubiquitous mediator of cell proliferation that transactivates the expression of various genes through E-box sites. Here we report a novel gene, mimitin (Myc-induced mitochondrial protein), that encodes a mitochondrial protein with a molecular mass of 20 kDa. We demonstrated that the transcription of mimitin is directly stimulated by c-Myc. To investigate the role of Mimitin, its expression was suppressed by the RNA interference (RNAi) technique. Whereas specific inhibition of mimitin expression did not affect cell proliferation in human cervical carcinoma, colon adenocarcinoma, and hepatocarcinoma cell lines, it did suppress cell proliferation in human glioblastoma, esophageal squamous cell carcinoma (ESCC), and embryonic lung fibroblastic cells, with the greatest suppression efficiency in ESCC cells. To investigate whether mimitin is related to tumorigenesis in ESCC in vivo, the expression of Mimitin protein in ESCC tissues was studied. Mimitin was highly expressed in 80% (28 of 35) of ESCC tumors, suggesting that high expression of Mimitin is a characteristic feature of ESCC. The expression level of Mimitin was found to be correlated with that of c-Myc and cell proliferation, but not with the histopathological grade, stage of cancer, or age of patients. Taken together, these results suggest that the novel gene mimitin is a direct transcriptional target of c-Myc, and is involved in Myc-dependent cell proliferation at least in ESCC cells.
引用
收藏
页码:19977 / 19985
页数:9
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