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Start Over Descriptor "testisin" Journal british journal of cancer
2 results on '"testisin"'

1. Hypermethylation of the 5' CpG island of the gene encoding the serine protease Testisin promotes its loss in testicular tumorigenesis.

Author

Manton, K J, Douglas, M L, Netzel-Arnett, S, Fitzpatrick, D R, Nicol, D L, Boyd, A W, Clements, J A, and Antalis, T M

Subjects
*PHOSPHOINOSITIDES, *CARCINOGENESIS, *AMINO acids, *CELL culture, *GENE expression, *GENETIC regulation, *DNA metabolism, *ANIMAL experimentation, *CASTRATION, *CELL lines, *DNA, *ENZYME inhibitors, *GENES, *GLYCOPROTEINS, *IMMUNOHISTOCHEMISTRY, *MEMBRANE proteins, *MICE, *POLYMERASE chain reaction, *PROTEOLYTIC enzymes, *TESTIS tumors, *XENOGRAFTS, *REVERSE transcriptase polymerase chain reaction, *DNA methylation, *SEQUENCE analysis
Abstract

The Testisin gene (PRSS21) encodes a glycosylphosphatidylinositol (GPI)-linked serine protease that exhibits testis tissue-specific expression. Loss of Testisin has been implicated in testicular tumorigenesis, but its role in testis biology and tumorigenesis is not known. Here we have investigated the role of CpG methylation in Testisin gene inactivation and tested the hypothesis that Testisin may act as a tumour suppressor for testicular tumorigenesis. Using sequence analysis of bisulphite-treated genomic DNA, we find a strong relationship between hypermethylation of a 385 bp 5' CpG rich island of the Testisin gene, and silencing of the Testisin gene in a range of human tumour cell lines and in 100% (eight/eight) of testicular germ cell tumours. We show that treatment of Testisin-negative cell lines with demethylating agents and/or a histone deacetylase inhibitor results in reactivation of Testisin gene expression, implicating hypermethylation in Testisin gene silencing. Stable expression of Testisin in the Testisin-negative Tera-2 testicular cancer line suppressed tumorigenicity as revealed by inhibition of both anchorage-dependent cell growth and tumour formation in an SCID mouse model of testicular tumorigenesis. Together, these data show that loss of Testisin is caused, at least in part, by DNA hypermethylation and histone deacetylation, and suggest a tumour suppressor role for Testisin in testicular tumorigenesis. [ABSTRACT FROM AUTHOR]

Published
2005
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2. Hypermethylation of the 5′ CpG island of the gene encoding the serine protease Testisin promotes its loss in testicular tumorigenesis

Author

Meaghan L. Douglas, Sarah Netzel-Arnett, Andrew W. Boyd, Kerry J. Manton, David Fitzpatrick, Judith A. Clements, Toni M. Antalis, and David Nicol

Subjects
Adult, Male, Cancer Research, tumour suppressor, Tumor suppressor gene, medicine.drug_class, serine protease, Transplantation, Heterologous, Mice, SCID, medicine.disease_cause, GPI-Linked Proteins, Mice, Testicular Neoplasms, Cell Line, Tumor, medicine, Gene silencing, Animals, Humans, Gene Silencing, Molecular Diagnostics, Regulation of gene expression, biology, Reverse Transcriptase Polymerase Chain Reaction, Histone deacetylase inhibitor, Serine Endopeptidases, Membrane Proteins, DNA, Neoplasm, Sequence Analysis, DNA, DNA Methylation, Molecular biology, Immunohistochemistry, Testisin, Gene Expression Regulation, Neoplastic, Histone Deacetylase Inhibitors, Histone, Oncology, CpG site, DNA methylation, biology.protein, CpG Islands, methylation, Carcinogenesis, Corrigendum, Orchiectomy
Abstract

The Testisin gene (PRSS21) encodes a glycosylphosphatidylinositol (GPI)-linked serine protease that exhibits testis tissue-specific expression. Loss of Testisin has been implicated in testicular tumorigenesis, but its role in testis biology and tumorigenesis is not known. Here we have investigated the role of CpG methylation in Testisin gene inactivation and tested the hypothesis that Testisin may act as a tumour suppressor for testicular tumorigenesis. Using sequence analysis of bisulphite-treated genomic DNA, we find a strong relationship between hypermethylation of a 385 bp 5′ CpG rich island of the Testisin gene, and silencing of the Testisin gene in a range of human tumour cell lines and in 100% (eight/eight) of testicular germ cell tumours. We show that treatment of Testisin-negative cell lines with demethylating agents and/or a histone deacetylase inhibitor results in reactivation of Testisin gene expression, implicating hypermethylation in Testisin gene silencing. Stable expression of Testisin in the Testisin-negative Tera-2 testicular cancer line suppressed tumorigenicity as revealed by inhibition of both anchorage-dependent cell growth and tumour formation in an SCID mouse model of testicular tumorigenesis. Together, these data show that loss of Testisin is caused, at least in part, by DNA hypermethylation and histone deacetylation, and suggest a tumour suppressor role for Testisin in testicular tumorigenesis.

Published
2015

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