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Programmed cell death‐10 enhances proliferation and protects malignant T cells from apoptosis
Author(s) -
LAUENBORG BRITT,
KOPP KATHARINA,
KREJSGAARD THORBJØRN,
ERIKSEN KARSTEN W.,
GEISLER CARSTEN,
DABELSTEEN SALLY,
GNIADECKI ROBERT,
ZHANG QIAN,
WASIK MARIUSZ A.,
WOETMANN ANDERS,
ODUM NIELS
Publication year - 2010
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2010.02669.x
Subject(s) - apoptosis , biology , cell growth , programmed cell death , signal transduction , activator (genetics) , kinase , microbiology and biotechnology , cancer research , gene , biochemistry
Lauenborg B, Kopp K, Krejsgaard T, Eriksen KW, Geisler C, Dabelsteen S, Gniadecki R, Zhang Q, Wasik MA, Woetmann A, Odum N. Programmed cell death‐10 enhances proliferation and protects malignant T cells from apoptosis. APMIS 2010; 118: 719–28. The programmed cell death‐10 (PDCD10; also known as cerebral cavernous malformation‐3 or CCM3) gene encodes an evolutionarily conserved protein associated with cell apoptosis. Mutations in PDCD10 result in cerebral cavernous malformations, an important cause of cerebral hemorrhage. PDCD10 is associated with serine/threonine kinases and phosphatases and modulates the extracellular signal‐regulated kinase pathway suggesting a role in the regulation of cellular growth. Here we provide evidence of a constitutive expression of PDCD10 in malignant T cells and cell lines from peripheral blood of cutaneous T‐cell lymphoma (Sezary syndrome) patients. PDCD10 is associated with protein phosphatase‐2A, a regulator of mitogenesis and apoptosis in malignant T cells. Inhibition of oncogenic signal pathways [Jak3, Notch1, and nuclear factor‐κB (NF‐κB)] partly inhibits the constitutive PDCD10 expression, whereas an activator of Jak3 and NF‐κB, interleukin‐2 (IL‐2), enhances PDCD10 expression. Functional data show that PDCD10 depletion by small interfering RNA induces apoptosis and decreases proliferation of the sensitive cells. To our knowledge, these data provide the first functional link between PDCD10 and cancer.