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The Phosphatase And Tensin Homolog Deleted On Chromosome 10 (PTEN) regulates the phosphoinositol-3-kinase (PI3K)-AKT signaling pathway. In a series of 34 patients with PTEN mutations, we described gastrointestinal lymphoid hyperplasia, extensive hyperplastic tonsils, thymus hyperplasia, autoimmune lymphocytic thyroiditis, autoimmune hemolytic anemia, and colitis. Functional analysis of the gastrointestinal mucosa-associated lymphoid tissue revealed increased signaling via the PI3K-AKT pathway, including phosphorylation of S6 and increased cell proliferation, but also reduced apoptosis of CD20(+)CD10(+) B cells. Reduced activity of PTEN therefore affects homeostasis of human germinal center B cells by increasing PI3K-AKT signaling via mammalian target of rapamycin as well as antiapoptotic signals.

Original publication

DOI

10.1053/j.gastro.2012.01.011

Type

Journal article

Journal

Gastroenterology

Publication Date

05/2012

Volume

142

Pages

1093 - 1096.e6

Keywords

Adolescent, Adult, Autoimmune Diseases, B-Lymphocytes, Child, Child, Preschool, Female, Giant Lymph Node Hyperplasia, Hamartoma Syndrome, Multiple, Homeostasis, Humans, Intestinal Diseases, Male, Middle Aged, Mutation, PTEN Phosphohydrolase, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction