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

Antonio Di Cristofano, Paraskevi Kotsi, Yu Feng Peng, Carlos Cordon-Cardo, Keith B. Elkon, Pier Paolo Pandolfi

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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.

Original languageEnglish (US)
Pages (from-to)2122-2125
Number of pages4
JournalScience
Volume285
Issue number5436
DOIs
StatePublished - Oct 5 1999
Externally publishedYes

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Cite this

Di Cristofano, A., Kotsi, P., Peng, Y. F., Cordon-Cardo, C., Elkon, K. B., & Pandolfi, P. P. (1999). Impaired Fas response and autoimmunity in Pten(+/-) mice. Science, 285(5436), 2122-2125. https://doi.org/10.1126/science.285.5436.2122