Haploinsufficiency of the Pten Tumor Suppressor Gene Promotes Prostate Cancer Progression

The PTEN gene encodes a lipid phosphatase that negatively regulates the phosphatidylinositol 3-kinase pathway and is inactivated in a wide variety of malignant neoplasms. High rates of loss of heterozygosity are observed at the 10q23.3 region containing the human PTEN gene in prostate cancer and oth...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2001-09, Vol.98 (20), p.11563-11568
Main Authors: Kwabi-Addo, Bernard, Giri, Dipak, Schmidt, Karen, Podsypanina, Katrina, Parsons, Ramon, Greenberg, Norman, Ittmann, Michael
Format: Article
Language:English
Subjects:
Alleles
Animals
Biological Sciences
Cancer
chromosome 10
Chromosomes
Disease Progression
Genes
Genes, Tumor Suppressor
Genetic loci
Genetic mutation
Genetics
Humans
Male
Mice
Mice, Knockout
Phosphoric Monoester Hydrolases - deficiency
Phosphoric Monoester Hydrolases - genetics
Polymerase chain reaction
Prostate cancer
prostate carcinoma
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Pten gene
PTEN Phosphohydrolase
Survival Rate
Tumor Suppressor Proteins - deficiency
Tumor Suppressor Proteins - genetics
Tumors
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Summary:The PTEN gene encodes a lipid phosphatase that negatively regulates the phosphatidylinositol 3-kinase pathway and is inactivated in a wide variety of malignant neoplasms. High rates of loss of heterozygosity are observed at the 10q23.3 region containing the human PTEN gene in prostate cancer and other human malignancies, but the demonstrated rate of biallelic inactivation of the PTEN gene by mutation or homozygous deletion is significantly lower than the rate of loss of heterozygosity. The transgenic adenocarcinoma of mouse prostate model is a well characterized animal model of prostate cancer. Analysis of prostate cancer progression in transgenic adenocarcinoma of mouse prostate mice bred to Pten+/-heterozygous mice, coupled with analysis of the Pten gene and protein in the resulting tumors, reveals that haploinsufficiency of the Pten gene promotes the progression of prostate cancer in this model system. This observation provides a potential explanation for the discordance in rates of loss of heterozygosity at 10q23 and biallelic PTEN inactivation observed in prostate cancer and many human malignancies.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.201167798