Frequent silencing of the GPC3 gene in ovarian cancer cell lines

GPC3 encodes a glypican integral membrane protein and is mutated in the Simpson-Golabi-Behmel syndrome. Simpson-Golabi-Behmel syndrome, an X-linked condition, is characterized by pre- and postnatal overgrowth as well as by various other abnormalities, including increased risk of embryonal tumors. Th...

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Published inCancer research (Chicago, Ill.) Vol. 59; no. 4; pp. 807 - 810
Main Authors HSINGCHI LIN, HUBER, R, SCHLESSINGER, D, MORIN, P. J
Format Journal Article
LanguageEnglish
Published Philadelphia, PA American Association for Cancer Research 15.02.1999
Subjects
Biological and medical sciences
DNA Methylation
Female
Female genital diseases
Genes, Tumor Suppressor
Glypicans
Gynecology. Andrology. Obstetrics
Heparan Sulfate Proteoglycans
Heparitin Sulfate - genetics
Humans
Medical sciences
Ovarian Neoplasms - genetics
Promoter Regions, Genetic
Proteoglycans - genetics
Tumor Cells, Cultured
Tumors
Human
Gene product
Transcription promoter
Malignant tumor
Gene expression
In vitro
Female genital diseases
Ovarian diseases
Ovary
Gene silencing
Established cell line
Tumor progression
Mutation
Methylation
Tumor cell
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Summary:GPC3 encodes a glypican integral membrane protein and is mutated in the Simpson-Golabi-Behmel syndrome. Simpson-Golabi-Behmel syndrome, an X-linked condition, is characterized by pre- and postnatal overgrowth as well as by various other abnormalities, including increased risk of embryonal tumors. The GPC3 gene is located at Xq26, a region frequently deleted in advanced ovarian cancers. To determine whether GPC3 is a tumor suppressor in ovarian neoplasia, we studied its expression and mutational status in 13 ovarian cancer cell lines. No mutations were found in GPC3, but its expression was lost in four (31%) of the cell lines analyzed. In an of the cases where GPC3 expression was lost, the GPC3 promoter was hypermethylated, as demonstrated by Southern analysis. Expression of GPC3 was restored by treatment of the cells with the demethylating agent 5-aza-2'-deoxycytidine. A colony-forming assay confirmed that ectopic GPC3 expression inhibited the growth of ovarian cancer cell lines. Our results show that GPC3, a gene involved in the control of organ growth, is frequently inactivated in a subset of ovarian cancers and suggest that it may function as a tumor suppressor in the ovary.
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ISSN:0008-5472
1538-7445