ESE-1 inhibits the invasion of oral squamous cell carcinoma in conjunction with MMP-9 suppression.

Abstract

OBJECTIVES:

Matrix metalloproteinases (MMPs) regulated by ets transcription factors facilitate carcinoma cell invasion. An ets family member, ESE-1, is expressed specifically in epithelial tissues, but its association with MMPs is obscure. In this study, we investigated whether ESE-1 regulates invasion of oral squamous cell carcinoma (SCC) via transcriptional activity of MMP-9.

METHODS:

HSC-3 and KB were used as human oral SCC lines. The expression of ESE-1 and MMP-9 was detected by in situ hybridization and immunohistochemistry. Invasion assay, gelatin zymography and Northern blotting were used to detect the invasion activity, the gelatinolytic activity and the expression of MMP-9 in the ESE-1 transfectants. Luciferase assays and mutation analysis were used for the transcriptional analysis of MMP-9 promoter region by ESE-1.

RESULTS:

ESE-1 was expressed in the intermediate layer but not in the invasive area, in which MMP-9 was expressed, in the oral SCC tissues. ESE-1 suppressed invasion activity and 92 kDa gelatinolytic activity in HSC-3 as a result of transfection. ESE-1 regulates MMP-9 expression in a negative manner and the ets binding site on the MMP-9 promoter contributed to suppression by ESE-1.

CONCLUSIONS:

These findings indicate that ESE-1 negatively regulates the invasion of oral SCC via transcriptional suppression of MMP-9.

• Authors: S Iwai, S Amekawa, K Yomogida, T Sumi, M Nakazawa, Y Yura, Y Nishimune, M Nozaki
• Journal: Oral diseases (Oral Dis) Vol. 14 Issue 2 Pg. 144-9 (Mar 2008) ISSN: 1354-523X [Print] Denmark
• PMID: 18302674 (Publication Type: Journal Article)

Chemical References

• DNA-Binding Proteins
• ELF3 protein, human
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-ets
• RNA, Messenger
• Transcription Factors
• Matrix Metalloproteinase 9

Topics

• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Line, Tumor
• DNA-Binding Proteins (genetics, metabolism)
• Gene Expression Regulation, Neoplastic (physiology)
• Humans
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mouth Neoplasms (metabolism, pathology)
• Neoplasm Invasiveness
• Proto-Oncogene Proteins (genetics, metabolism)
• Proto-Oncogene Proteins c-ets
• RNA, Messenger (analysis)
• Transcription Factors (genetics, metabolism)
• Transcription, Genetic (physiology)