Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma Journal Article
| Authors: | Murthy, S. S.; Shen, T.; De Rienzo, A.; Lee, W. C.; Ferriola, P. C.; Jhanwar, S. C.; Mossman, B. T.; Filmus, J.; Testa, J. R. |
| Article Title: | Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma |
| Abstract: | Gene expression changes in rat asbestos-induced malignant mesothelioma (MM) cells were investigated by differential mRNA display. A mRNA transcript identified by this approach was abundant in normal rat mesothelial cells but not expressed in rat MM cell lines. Northern blot analysis confirmed that this transcript is uniformly silenced in rat MM cell lines and primary tumors. Nucleotide sequence analysis revealed that this transcript is encoded by the rat glypican 3 gene (GPC3), whose human homolog is mutated in the Simpson-Golabi-Behmel overgrowth syndrome. Allelic loss at the GPC3 locus was infrequent (6.9) in MM cell lines, and no mutations were found. GPC3 transcript levels mere markedly decreased in 16 of 18 primary tumors and 17 of 22 human MM cell lines. Most of the cell lines mere shown to have aberrant methylation of the GPC3 promoter region. In two of four human MM cell lines tested, GPC3 expression was restored after 2-deoxy 5-azacytidine (DAC)-mediated demethylation of its promoter region. Ectopic expression of CPC3 inhibited in vitro colony formation of human MM cells. Collectively, these data suggest that down-regulation of GPC3 is a common occurrence in MM and that GPC3, an X-linked recessive overgrowth gene, may encode a negative regulator of mesothelial cell growth. |
| Keywords: | human cell; promoter region; nonhuman; animal cell; animals; allele; gene expression; cell growth; cell line; animal experiment; animal model; down-regulation; gene locus; alleles; dna methylation; animalia; tumor suppressor gene; messenger rna; nucleotide sequence; rat; malignant mesothelioma; mesothelioma; gene loss; down regulation; rats; gene silencing; sequence homology; azacitidine; heparitin sulfate; mesothelium cell; dna, complementary; northern blotting; rats, inbred f344; promoter methylation; asbestos; gene regulation; promoter regions (genetics); proteoglycans; proteoglycan; x chromosome linkage; humans; human; female; priority journal; article; heparan sulfate proteoglycans; glypican; differential mrna display; simpson golabi behmel syndrome; glypicans |
| Journal Title: | Oncogene |
| Volume: | 19 |
| Issue: | 3 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2000-01-20 |
| Start Page: | 410 |
| End Page: | 416 |
| Language: | English |
| PUBMED: | 10656689 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
