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Bikunin Target Genes in Ovarian Cancer Cells Identified by Microarray Analysis
- Source :
- Journal of Biological Chemistry. 278:14640-14646
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- Bikunin, a Kunitz-type protease inhibitor, could potentially suppress tumor cell invasion and metastasis. Our previous study revealed that overexpression of bikunin in a human ovarian cancer cell line, HRA, resulted in a down-regulation in uPA and uPAR gene expression. For identifying the full repertoire of bikunin-regulated genes, a cDNA microarray hybridization screening was conducted using mRNA from bikunin-treated or bikunin-transfected HRA cells. A number of bikunin-regulated genes were identified, and their regulation was confirmed by Northern blot analysis. Our screen identified 11 bikunin-stimulated genes and 29 bikunin-repressed genes. The identified genes can indeed be classified into distinct subsets. These include transcriptional regulators, oncogenes/tumor suppressor genes, signaling molecules, growth/cell cycle, invasion/metastasis, cytokines, apoptosis, ion channels, extracellular matrix proteins, as well as some proteases. This screen identified suppression of several genes such as CDC-like kinase, LIM domain binding, Ets domain transcription factor, Rho GTPase-activating protein, tyrosine phosphorylation-regulated kinase, hyaluronan-binding protein, matriptase, and pregnancy-associated plasma protein-A (PAPP-A), which have previously been implicated in enhancing tumor promotion. Northern blot analysis confirmed that several genes including matriptase and PAPP-A were down-regulated by bikunin by approximately 9-fold. Further, genetic inhibition of matriptase or PAPP-A could lead to diminished invasion. These results show that bikunin alters the pattern of gene expression in HRA cells leading to a block in cell invasion.
- Subjects :
- Cell signaling
Serine Proteinase Inhibitors
Biology
Transfection
Biochemistry
Cell Movement
Gene expression
Tumor Cells, Cultured
Humans
Pregnancy-Associated Plasma Protein-A
Trypsin
Matriptase
Northern blot
Molecular Biology
Transcription factor
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms
Membrane Glycoproteins
Microarray analysis techniques
Gene Expression Profiling
Serine Endopeptidases
Cell Biology
Cell cycle
Molecular biology
Cell biology
Gene Expression Regulation
biology.protein
Female
Tumor promotion
Trypsin Inhibitor, Kunitz Soybean
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 278
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....d6ad9b94508ef4152d6ab0490944a06d