Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma
- 20 January 2000
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 19 (3), 410-416
- https://doi.org/10.1038/sj.onc.1203322
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 were markedly decreased in 16 of 18 primary tumors and 17 of 22 human MM cell lines. Most of the cell lines were 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 GPC3 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
This publication has 20 references indexed in Scilit:
- OCI-5/GPC3, a Glypican Encoded by a Gene That Is Mutated in the Simpson-Golabi-Behmel Overgrowth Syndrome, Induces Apoptosis in a Cell Line–specific MannerThe Journal of cell biology, 1998
- Stimulation of fibroblast growth factor receptor-1 occupancy and signaling by cell surface-associated syndecans and glypican.The Journal of cell biology, 1996
- Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndromeNature Genetics, 1996
- High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas.Proceedings of the National Academy of Sciences of the United States of America, 1995
- Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.Proceedings of the National Academy of Sciences of the United States of America, 1994
- Maspin, a Serpin with Tumor-Suppressing Activity in Human Mammary Epithelial CellsScience, 1994
- Differential Display of Eukaryotic Messenger RNA by Means of the Polymerase Chain ReactionScience, 1992
- Suppression of Human Colorectal Carcinoma Cell Growth by Wild-Type p53Science, 1990
- Asbestos-Related DiseasesNew England Journal of Medicine, 1989
- Diffuse Pleural Mesothelioma and Asbestos Exposure in the North Western Cape ProvinceOccupational and Environmental Medicine, 1960