Abstract
Glypican-3 (GPC3) is a membrane-bound heparan sulfate proteoglycan that is mutated in the Simpson-Golabi-Behmel syndrome. This is an X-linked condition characterized by overgrowth, and various visceral and skeletal dysmorphisms. The phenotype of the Simpson-Golabi-Behmel syndrome patients and GPC3-deficient mice, as well as gene transfection experiments indicate that GPC3 can act as an inhibitor of cell proliferation and survival. It has been previously shown that GPC3 expression is downregulated in mesotheliomas and ovarian cancer. Here we report that GPC3 expression is also silenced in human breast cancer, and that this silencing is due, at least in part, to hypermethylation of the GPC3 promoter. Ectopic expression of GPC3 inhibited growth in eight out of 10 breast cancer cell lines. Collectively, these data suggest that GPC3 can act as a negative regulator of breast cancer growth.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Azacitidine / analogs & derivatives*
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Azacitidine / pharmacology
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Breast / metabolism
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / pathology
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DNA Methylation* / drug effects
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DNA, Neoplasm / chemistry
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DNA, Neoplasm / genetics*
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Decitabine
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Dosage Compensation, Genetic
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Epithelial Cells / metabolism
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Female
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Gene Expression Regulation, Neoplastic* / drug effects
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Gene Silencing*
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Genes, Tumor Suppressor*
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Glypicans
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Heparan Sulfate Proteoglycans / biosynthesis
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Heparan Sulfate Proteoglycans / genetics*
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Humans
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Liver Neoplasms / genetics
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Liver Neoplasms / pathology
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Loss of Heterozygosity
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics*
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Promoter Regions, Genetic / genetics*
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
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Tumor Stem Cell Assay
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X Chromosome / genetics
Substances
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DNA, Neoplasm
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Glypicans
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Heparan Sulfate Proteoglycans
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Neoplasm Proteins
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Decitabine
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Azacitidine