Functional characterization of proximal promoter of gene for human BRAK/CXCL14, a tumor-suppressing chemokine

• Komori Reika

  Oral Health Science Research Center, Kanagawa Dental College Department of Biochemistry and Molecular Biology, Kanagawa Dental College Department of Pediatric Dentistry, Kanagawa Dental College

• Ozawa Shigeyuki

  Oral Health Science Research Center, Kanagawa Dental College Department of Biochemistry and Molecular Biology, Kanagawa Dental College Department of Oral and Maxillofacial Surgery, Kanagawa Dental College

• Kato Yasumasa

  Oral Health Science Research Center, Kanagawa Dental College Department of Biochemistry and Molecular Biology, Kanagawa Dental College

• Shinji Hisaaki

  Department of Pediatric Dentistry, Kanagawa Dental College

• Kimoto Shigenari

  Department of Pediatric Dentistry, Kanagawa Dental College

• Hata Ryu-Ichiro

  Oral Health Science Research Center, Kanagawa Dental College Department of Biochemistry and Molecular Biology, Kanagawa Dental College

抄録

BRAK/CXCL14 is a chemokine that is expressed in many normal cells and tissues but is absent from or expressed at very low levels in transformed cells and cancerous tissues including head and neck squamous cell carcinoma (HNSCC). We reported previously that the forced expression of BRAK/CXCL14 in HNSCC cells decreased the rate of tumor formation and size of tumor xenografts in athymic nude mice and SCID mice, suggesting that expression level of the gene is important for tumor suppression. In order to study the regulatory mechanisms governing the expression of this gene, we determined the transcriptional start site and promoter motifs of the gene. The major transcriptional start site determined by 5'rapid amplification of cDNA end method was located 283 bp downstream of the first proposed site of the gene. Determination of luciferase activities of reporter gene constructs with various deletions or mutations showed that an atypical TATA-like sequence, TATTAA was essential for the transcription of the gene and that the AP-1 binding sequence and tandem GC box were necessary for stimulating the expression of the gene in human squamous epithelial cells. The human DNA region was highly homologous (95% base identity) to the mouse gene. In addition, okadaic acid, an inhibitor of serine/threonine phosphatases 1, 2A and 2B, stimulated TATTAA sequence and AP-1 binding-sequence dependent promoter activity as well as increased the level of BRAK/CXCL14 mRNA, indicating that these sequences are essential for the regulation of BRAK/CXCL14 gene expression in the cells.

収録刊行物

• Biomedical Research

  Biomedical Research 31 (2), 123-131, 2010

  バイオメディカルリサーチプレス

キーワード

• General Biochemistry, Genetics and Molecular Biology
• General Medicine

詳細情報

• CRID: 1390001204901668352
• NII論文ID: 130004903789
• DOI: 10.2220/biomedres.31.123
• ISSN: 1880313X
• ISSN: 03886107
• Web Site: https://search.jamas.or.jp/link/ui/2010293530
• 本文言語コード: en
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• 抄録ライセンスフラグ: 使用不可