Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression
- 28 April 1998
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 95 (9), 5246-5250
- https://doi.org/10.1073/pnas.95.9.5246
Abstract
The recently identified PTEN/MMAC1 gene is a candidate tumor suppressor implicated in multiple tumor types based on mutations or homozygous deletions of the gene in certain human cancers. No studies of PTEN/MMAC1 mRNA or protein expression in cancer cells have been reported, primarily because of significant numbers of normal cells contaminating most tumor samples and because of the lack of antibody reagents. We examined PTEN/MMAC1 in advanced prostate cancer for gene mutations or abnormalities in expression by using a series of recently derived xenografts free of normal human cells and a PTEN/MMAC1-specific antibody. Only 1 of 10 tumors contained a homozygous deletion of PTEN/MMAC1, and no mutations were detected in the entire coding region of the remaining nine xenografts. However, five of these showed reduced or absent PTEN/MMAC1 expression by Northern analysis and reverse transcription–PCR of mRNA. PTEN/MMAC1 mRNA expression was restored in nonexpressing prostate cancer cells by in vitro treatment with the demethylating agent 5-azadeoxycytidine. Alterations in PTEN/MMAC1 expression were confirmed at the protein level by immunoblot analysis, and immunohistochemical studies show that the endogenous wild-type PTEN/MMAC1 protein is localized exclusively in the cytoplasm. These results demonstrate that loss of PTEN/MMAC1 expression occurs frequently in advanced prostate cancer.Keywords
This publication has 26 references indexed in Scilit:
- PTEN1 is frequently mutated in primary endometrial carcinomasNature Genetics, 1997
- Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndromeNature Genetics, 1997
- Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancersNature Genetics, 1997
- PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate CancerScience, 1997
- Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomasNature Medicine, 1997
- An STS-Based Map of the Human GenomeScience, 1995
- Frequency of homozygous deletion at p16/CDKN2 in primary human tumoursNature Genetics, 1995
- Role of the Ubiquitin-Proteasome Pathway in Regulating Abundance of the Cyclin-Dependent Kinase Inhibitor p27Science, 1995
- 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancersNature Medicine, 1995
- Rates of p16 ( MTS1 ) Mutations in Primary Tumors with 9p LossScience, 1994