Shortened microsatellite d(CA)21 sequence down‐regulates promoter activity of matrix metalloproteinase 9 gene

FEBS Letters

Shimajiri, Shohei²  Murata, Yoshitake¹  Sasaguri, Yasuyuki²  Wang, Ke-Yong²  Arima, Nobuyuki²  Hamada, Tetsuo²  Tanimoto, Akihide² 

[1] Kyurin Omtest Laboratory Department, Kyurin Corporation, Yahatanishi-ku, Kitakyushu 806-0046, Japan;Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental of Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan

关键词: Microsatellite;    d(CA) repeat;    Matrix metalloproteinase 9;    Gene transcription;    Esophageal cancer;    MMP-9;    matrix metalloproteinase 9;    EGF;    epidermal growth factor;    PCR;    polymerase chain reaction;    DMEM;    Dulbecco's modified Eagle's medium;    FCS;    fetal calf serum;    EMSA;    electrophoretic mobility shift assay;   

DOI  :  10.1016/S0014-5793(99)00863-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

One characteristic elements in the promoter of the matrix metalloproteinase 9 (MMP-9) gene is the d(CA) repeat. To investigate whether this element regulates the transcription of the MMP-9 gene and its enzymatic activities, we sequenced the promoter region isolated from esophageal carcinoma cell lines. TE9 cells with low MMP-9 enzymatic activity had the number of d(CA) repeats shortened from 21 to 14 or 18. TE8, TE10 and TE11 cells with high MMP-9 activities had 21 or 23 d(CA) repeats. Luciferase assays using MMP-9 promoter containing 18, 14 or 0 d(CA) repeats showed transcriptional activities which were 50, 50 or 5%, respectively, of the level achieved with promoter containing 21 d(CA) repeats. Sequence analysis of the promoter of 223 Japanese subjects revealed that most had two alleles with 20, 21 or 22 d(CA) repeats, whereas six had one or two alleles with 14, 18 or 19 d(CA) repeats. We postulate that length alteration of the d(CA) repeat causes phenotypic differences among carcinoma cells and that microsatellite instability may contribute to the polymorphism of d(CA) repeat length.

【 授权许可】

Unknown