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

• Published in: FEBS letters Vol. 455; no. 1; pp. 70 - 74
• Main Authors: Shimajiri, Shohei, Arima, Nobuyuki, Tanimoto, Akihide, Murata, Yoshitake, Hamada, Tetsuo, Wang, Ke-Yong, Sasaguri, Yasuyuki
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 16.07.1999
• Subjects: Base Sequence; Cell Nucleus - metabolism; Collagenases - genetics; d(CA) repeat; DMEM, Dulbecco's modified Eagle's medium; DNA; Down-Regulation; EGF, epidermal growth factor; EMSA, electrophoretic mobility shift assay; Esophageal cancer; FCS, fetal calf serum; Gene transcription; Luciferases - genetics; Matrix Metalloproteinase 9; Microsatellite; Microsatellite Repeats - genetics; MMP-9, matrix metalloproteinase 9; Molecular Sequence Data; PCR, polymerase chain reaction; Promoter Regions, Genetic; Tumor Cells, Cultured; Microsatellite; Matrix metalloproteinase 9; DMEM, Dulbecco’s modified Eagle’s medium; EGF, epidermal growth factor; d(CA) repeat; PCR, polymerase chain reaction; EMSA, electrophoretic mobility shift assay; Esophageal cancer; MMP-9, matrix metalloproteinase 9; Gene transcription; FCS, fetal calf serum
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)00863-7

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.