TY - JOUR
T1 - Impaired Fas response and autoimmunity in Pten(+/-) mice
AU - Di Cristofano, Antonio
AU - Kotsi, Paraskevi
AU - Peng, Yu Feng
AU - Cordon-Cardo, Carlos
AU - Elkon, Keith B.
AU - Pandolfi, Pier Paolo
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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U2 - 10.1126/science.285.5436.2122
DO - 10.1126/science.285.5436.2122
M3 - Article
C2 - 10497129
AN - SCOPUS:0032843540
SN - 0036-8075
VL - 285
SP - 2122
EP - 2125
JO - Science
JF - Science
IS - 5436
ER -