Abstract
Mapping of homozygous deletions on human chromosome 10q23 has led to the isolation of a candidate tumor suppressor gene, PTEN, that appears to be mutated at considerable frequency in human cancers. In preliminary screens, mutations of PTEN were detected in 31% (13/42) of glioblastoma cell lines and xenografts, 100% (4/4) of prostate cancer cell lines, 6% (4/65) of breast cancer cell lines and xenografts, and 17% (3/18) of primary glioblastomas. The predicted PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions. These homologies suggest that PTEN may suppress tumor cell growth by antagonizing protein tyrosine kinases and may regulate tumor cell invasion and metastasis through interactions at focal adhesions.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Brain Neoplasms / genetics
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Breast Neoplasms / genetics
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Chromosome Mapping
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Chromosomes, Human, Pair 10*
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Female
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Frameshift Mutation
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Genes, Tumor Suppressor*
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Glioblastoma / genetics
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Humans
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Male
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Microfilament Proteins / chemistry
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Molecular Sequence Data
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Mutation*
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Neoplasm Transplantation
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Neoplasms / genetics*
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PTEN Phosphohydrolase
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Phosphoric Monoester Hydrolases*
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Phosphotyrosine / metabolism
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Prostatic Neoplasms / genetics
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / genetics*
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Protein Tyrosine Phosphatases / physiology
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Sequence Deletion
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Sequence Homology, Amino Acid
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Tensins
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Transplantation, Heterologous
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
Substances
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Microfilament Proteins
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Tensins
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Tumor Suppressor Proteins
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Phosphotyrosine
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Protein-Tyrosine Kinases
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Phosphoric Monoester Hydrolases
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Protein Tyrosine Phosphatases
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PTEN Phosphohydrolase
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PTEN protein, human