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Bikunin target genes in ovarian cancer cells identified by microarray analysis
Mika Suzuki1, Hiroshi Kobayashi, Yoshiko Tanaka
1Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka 431-3192, Japan.
The Journal of Biological Chemistry
|February 7, 2003
Summary
Bikunin, a protease inhibitor, suppresses ovarian cancer cell invasion by down-regulating key genes involved in tumor promotion. This study identified specific bikunin-regulated genes, offering new therapeutic targets for inhibiting metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Bikunin is a Kunitz-type protease inhibitor with potential anti-cancer properties.
- Previous research indicated bikunin down-regulates urokinase plasminogen activator (uPA) and its receptor (uPAR) in ovarian cancer cells.
- Understanding the full range of bikunin-regulated genes is crucial for elucidating its anti-metastatic mechanisms.
Purpose of the Study:
- To identify the complete set of genes regulated by bikunin in human ovarian cancer cells (HRA).
- To confirm the regulation of identified genes using Northern blot analysis.
- To investigate the role of specific bikunin-repressed genes in tumor invasion.
Main Methods:
- cDNA microarray hybridization screening of mRNA from bikunin-treated or -transfected HRA cells.
- Northern blot analysis for confirmation of gene expression changes.
- Genetic inhibition of specific target genes (matriptase, PAPP-A) to assess invasion.
Main Results:
- Identified 11 bikunin-stimulated and 29 bikunin-repressed genes.
- Suppression of genes implicated in tumor promotion, including matriptase and pregnancy-associated plasma protein-A (PAPP-A), by approximately 9-fold.
- Genetic inhibition of matriptase or PAPP-A led to reduced cancer cell invasion.
Conclusions:
- Bikunin significantly alters gene expression patterns in ovarian cancer cells.
- Down-regulation of specific genes like matriptase and PAPP-A by bikunin contributes to the inhibition of cell invasion and metastasis.
- Bikunin demonstrates potential as a therapeutic agent for ovarian cancer by blocking invasion pathways.