Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis

TY - JOUR

T1 - Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis

AU - Lauenborg, Britt

AU - Kopp, Katharina

AU - Krejsgaard, Thorbjørn

AU - Eriksen, Karsten W

AU - Geisler, Carsten

AU - Dabelsteen, Sally

AU - Gniadecki, Robert

AU - Zhang, Qian

AU - Wasik, Mariusz A

AU - Andersen, Anders Woetmann

AU - Odum, Niels

N1 - © 2010 The Authors. Journal Compilation © 2010 APMIS.

PY - 2010/10/1

Y1 - 2010/10/1

N2 - 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 serinethreonine 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-B (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.

AB - 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 serinethreonine 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-B (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.

KW - Apoptosis

KW - Apoptosis Regulatory Proteins

KW - Cell Proliferation

KW - Humans

KW - Jurkat Cells

KW - Membrane Proteins

KW - Protein Phosphatase 2

KW - Proto-Oncogene Proteins

KW - RNA

KW - RNA, Small Interfering

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sezary Syndrome

KW - Signal Transduction

KW - Skin Neoplasms

KW - T-Lymphocytes

KW - Transfection

U2 - 10.1111/j.1600-0463.2010.02669.x

DO - 10.1111/j.1600-0463.2010.02669.x

M3 - Journal article

C2 - 20854465

SN - 0903-465X

VL - 118

SP - 719

EP - 728

JO - APMIS. Supplementum

JF - APMIS. Supplementum

IS - 10

ER -