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J. Biol. Chem., Vol. 280, Issue 20, 19977-19985, May 20, 2005

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A Novel Myc-target Gene, mimitin, That Is Involved in Cell Proliferation of Esophageal Squamous Cell Carcinoma^*

Makoto Tsuneoka, Kwesi Teye, Nobuyuki Arima¶, Mikiko Soejima, Hidenori Otera||, Kazuyo Ohashi**, Yasutoshi Koga, Hiromasa Fujita, Kazuo Shirouzu, Hiroshi Kimura¶¶, and Yoshiro Koda

From the Division of Human Genetics, Departments of Forensic Medicine, ^¶Pathology, Pediatrics and Child Health, and Surgery, Kurume University School of Medicine, Kurume 830-0011, Japan, the ^||Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan, the ^**Graduate School of Science and Technology, Chiba University, Chiba 263-8522, Japan, and the ^¶¶Chiba Institute of Science, Choshi 288-0025, Japan

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.

Received for publication, February 2, 2005 , and in revised form, March 15, 2005.

^* This work was supported by Grants-in-aid from the Ministry of Education, Science, and Culture of Japan 16570164 and the Osaka Cancer Research Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Table S1.

To whom correspondence should be addressed: Division of Human Genetics, Dept. of Forensic Science, Kurume University School of Medicine, Kurume 830-0011, Japan. Tel.: 81-942-31-7554; Fax: 81-942-31-7700; E-mail: tsuneoka{at}med.kurume-u.ac.jp.The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AB183433 (cDNA sequence for human Mimitin), AB183435 ((DNA sequence for the mimitin gene promoter), and AB183434 (cDNA sequence for mouse Mimitin).

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