Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis
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Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis. / Lauenborg, Britt; Kopp, Katharina; Krejsgaard, Thorbjørn; Eriksen, Karsten W; Geisler, Carsten; Dabelsteen, Sally; Gniadecki, Robert; Zhang, Qian; Wasik, Mariusz A; Andersen, Anders Woetmann; Odum, Niels.
In: Acta Pathologica Microbiologica et Immunologica Scandinavica, Vol. 118, No. 10, 01.10.2010, p. 719-28.Research output: Contribution to journal › Journal article › Research › peer-review
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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 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-¿B (NF-¿B)] partly inhibits the constitutive PDCD10 expression, whereas an activator of Jak3 and NF-¿B, 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 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-¿B (NF-¿B)] partly inhibits the constitutive PDCD10 expression, whereas an activator of Jak3 and NF-¿B, 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
VL - 118
SP - 719
EP - 728
JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
SN - 0903-4641
IS - 10
ER -
ID: 33732537