Impaired Fas response and autoimmunity in Pten(+/-) mice Journal Article

Authors: Di Cristofano, A.; Kotsi, P.; Peng, Y. F.; Cordon-Cardo, C.; Elkon, K. B.; Pandolfi, P. P.
Article Title: Impaired Fas response and autoimmunity in Pten(+/-) mice
Abstract: Inactivating mutations in the PTEN tumor suppressor gene, encoding a phosphatase, occur in three related human autosomal dominant disorders characterized by tumor susceptibility. Here it is shown that Pten heterozygous (Pten(+/-)) mutants develop a lethal polyclonal autoimmune disorder with features reminiscent of those observed in Fas-deficient mutants. Fas-mediated apoptosis was impaired in Pten(+/-) mice, and T lymphocytes from these mice show reduced activation-induced cell death and increased proliferation upon activation. Phosphatidylinositol (Pl) 3-kinase inhibitors restored Fas responsiveness in Pten(+/-) cells. These results indicate that Pten is an essential mediator of the Fas response and a repressor of autoimmunity and thus implicate the Pl 3-kinase/Akt pathway in Fas-mediated apoptosis.
Keywords: controlled study; proto-oncogene proteins; histopathology; nonhuman; cell proliferation; t lymphocyte; t-lymphocytes; mouse; animals; mice; cancer susceptibility; apoptosis; enzyme inhibition; phosphatase; fas antigen; animal experiment; animal model; phosphorylation; heterozygote; phosphatidylinositol 3 kinase; mice, inbred c57bl; animalia; b-lymphocytes; tumor suppressor gene; lymphocyte activation; immunoglobulin g; protein-serine-threonine kinases; tumor suppressor proteins; 1-phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; pten phosphohydrolase; autoimmunity; autoimmune diseases; phosphoric monoester hydrolases; t lymphocyte activation; antigen antibody complex; kidney glomerulus; antigens, cd95; kidney diseases; immune complex disease; male; female; priority journal; article; antibodies, antinuclear
Journal Title: Science
Volume: 285
Issue: 5436
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 1999-09-24
Start Page: 2122
End Page: 2125
Language: English
DOI: 10.1126/science.285.5436.2122
PUBMED: 10497129
PROVIDER: scopus
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
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