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

Research output: Contribution to journalArticle

439 Citations (Scopus)

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 - 1999
Externally publishedYes

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Phosphatidylinositol 3-Kinase
Autoimmunity
Apoptosis
Tumor Suppressor Genes
Phosphoric Monoester Hydrolases
Cell Death
T-Lymphocytes
Mutation
Neoplasms

ASJC Scopus subject areas

  • General

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

Impaired Fas response and autoimmunity in Pten(+/-) mice. / Di Cristofano, Antonio; Kotsi, Paraskevi; Peng, Yu Feng; Cordon-Cardo, Carlos; Elkon, Keith B.; Pandolfi, Pier Paolo.

In: Science, Vol. 285, No. 5436, 1999, p. 2122-2125.

Research output: Contribution to journalArticle

Di Cristofano, A, Kotsi, P, Peng, YF, Cordon-Cardo, C, Elkon, KB & Pandolfi, PP 1999, 'Impaired Fas response and autoimmunity in Pten(+/-) mice', Science, vol. 285, no. 5436, pp. 2122-2125. https://doi.org/10.1126/science.285.5436.2122
Di Cristofano A, Kotsi P, Peng YF, Cordon-Cardo C, Elkon KB, Pandolfi PP. Impaired Fas response and autoimmunity in Pten(+/-) mice. Science. 1999;285(5436):2122-2125. https://doi.org/10.1126/science.285.5436.2122
Di Cristofano, Antonio ; Kotsi, Paraskevi ; Peng, Yu Feng ; Cordon-Cardo, Carlos ; Elkon, Keith B. ; Pandolfi, Pier Paolo. / Impaired Fas response and autoimmunity in Pten(+/-) mice. In: Science. 1999 ; Vol. 285, No. 5436. pp. 2122-2125.
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