RECK negatively regulates matrix metalloproteinase-9 transcription

Area of Science:

• Molecular Biology
• Cancer Research
• Biochemistry

Background:

• Receptor regulated homobox (RECK) is a glycosylphosphatidylinositol-anchored glycoprotein.
• RECK is known to inhibit matrix metalloproteinases (MMPs), suppressing tumor cell metastasis.
• The precise mechanism of RECK's inhibitory action on MMPs remains unclear.

Purpose of the Study:

• To elucidate the molecular mechanism by which RECK suppresses tumor cell metastasis.
• To investigate the effect of RECK on matrix metalloproteinase-9 (MMP-9) gene expression and transcription.

Main Methods:

• Gene expression profiling comparing mock- and RECK-transfected HT1080 cells.
• Quantitative analysis of MMP-9 mRNA levels following RECK transfection and RECK-specific siRNA treatment.
• MMP-9 promoter assays to assess transcriptional activity.
• Analysis of transcription factor binding to the MMP-9 promoter.

Main Results:

• RECK significantly decreases matrix metalloproteinase-9 (MMP-9) mRNA levels.
• RECK-specific small interfering RNA (siRNA) increases MMP-9 mRNA in RECK-expressing cells.
• RECK suppresses MMP-9 promoter activity, requiring 12-O-tetradecanoylphorbol-13-acetate-responsive element (TRE) and kappaB sites.
• RECK inhibits the binding of Fra-1 and c-Jun transcription factors to the TRE within the MMP-9 promoter.

Conclusions:

• RECK acts as a negative regulator of matrix metalloproteinase-9 (MMP-9) transcription.
• The findings reveal a novel mechanism for RECK-mediated suppression of MMP-9, involving direct transcriptional inhibition.
• Understanding this mechanism provides insights into controlling tumor cell metastasis.