Publication Date:
1999-09-25
Description:
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 (PI) 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 PI 3-kinase/Akt pathway in Fas-mediated apoptosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Di Cristofano, A -- Kotsi, P -- Peng, Y F -- Cordon-Cardo, C -- Elkon, K B -- Pandolfi, P P -- AR45482/AR/NIAMS NIH HHS/ -- CA-08748/CA/NCI NIH HHS/ -- CA-82328/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2122-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics-Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10497129" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies, Antinuclear/blood
;
Antigens, CD95/*physiology
;
*Apoptosis
;
Autoimmune Diseases/*immunology/pathology
;
B-Lymphocytes/immunology/pathology
;
Female
;
Heterozygote
;
Immunoglobulin G/blood
;
Kidney Diseases/*immunology/pathology
;
Kidney Glomerulus/immunology/pathology
;
Lymphocyte Activation
;
Male
;
Mice
;
Mice, Inbred C57BL
;
PTEN Phosphohydrolase
;
Phosphatidylinositol 3-Kinases/antagonists & inhibitors/metabolism
;
Phosphoric Monoester Hydrolases/genetics/*physiology
;
Phosphorylation
;
*Protein-Serine-Threonine Kinases
;
Proto-Oncogene Proteins/metabolism
;
Proto-Oncogene Proteins c-akt
;
T-Lymphocytes/immunology/pathology
;
*Tumor Suppressor Proteins
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
