STAT1 acts as a tumor promoter for leukemia development

Boris Kovacic; Dagmar Stoiber; Richard Moriggl; Eva Weisz; René G Ott; Rita Kreibich; David E Levy; Hartmut Beug; Michael Freissmuth; Veronika Sexl

doi:10.1016/j.ccr.2006.05.025

STAT1 acts as a tumor promoter for leukemia development

Boris Kovacic, Dagmar Stoiber, Richard Moriggl, Eva Weisz, René G Ott, Rita Kreibich, David E Levy, Hartmut Beug, Michael Freissmuth, Veronika Sexl

Research output: Journal article (peer-reviewed) › Journal article

124 Citations (Scopus)

Abstract

The tumor suppressor STAT1 is considered a key regulator of the surveillance of developing tumors. Here, we describe an unexpected tumor-promoting role for STAT1 in leukemia. STAT1(-/-) mice are partially protected from leukemia development, and STAT1(-/-) tumor cells induce leukemia in RAG2(-/-) and immunocompetent mice with increased latency. The low MHC class I protein levels of STAT1(-/-) tumor cells enable efficient NK cell lysis and account for the enhanced tumor clearance. Strikingly, STAT1(-/-) tumor cells acquire increased MHC class I expression upon leukemia progression. These findings define STAT1 as a tumor promoter in leukemia development. Furthermore, we describe the upregulation of MHC class I expression as a general mechanism that allows for the escape of hematopoietic malignancies from immune surveillance.

Original language	English
Pages (from-to)	77-87
Number of pages	11
Journal	Cancer Cell
Volume	10
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2006.05.025
Publication status	Published - Jul 2006
Externally published	Yes

Keywords

Animals
B-Lymphocytes/metabolism
Cell Line, Tumor
Cell Proliferation
Cell Survival/genetics
Cell Transformation, Neoplastic/genetics
DNA-Binding Proteins/genetics
Disease Progression
Genotype
Histocompatibility Antigens Class I/immunology
Interferon-gamma/genetics
Killer Cells, Natural/immunology
Leukemia, Experimental/genetics
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Oncogene Proteins v-abl/genetics
Oncogene Proteins, Fusion/genetics
Phenotype
STAT1 Transcription Factor/deficiency
Stem Cells/metabolism
Survival Analysis

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10.1016/j.ccr.2006.05.025

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title = "STAT1 acts as a tumor promoter for leukemia development",

abstract = "The tumor suppressor STAT1 is considered a key regulator of the surveillance of developing tumors. Here, we describe an unexpected tumor-promoting role for STAT1 in leukemia. STAT1(-/-) mice are partially protected from leukemia development, and STAT1(-/-) tumor cells induce leukemia in RAG2(-/-) and immunocompetent mice with increased latency. The low MHC class I protein levels of STAT1(-/-) tumor cells enable efficient NK cell lysis and account for the enhanced tumor clearance. Strikingly, STAT1(-/-) tumor cells acquire increased MHC class I expression upon leukemia progression. These findings define STAT1 as a tumor promoter in leukemia development. Furthermore, we describe the upregulation of MHC class I expression as a general mechanism that allows for the escape of hematopoietic malignancies from immune surveillance.",

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author = "Boris Kovacic and Dagmar Stoiber and Richard Moriggl and Eva Weisz and Ott, {Ren{\'e} G} and Rita Kreibich and Levy, {David E} and Hartmut Beug and Michael Freissmuth and Veronika Sexl",

year = "2006",

month = jul,

doi = "10.1016/j.ccr.2006.05.025",

language = "English",

volume = "10",

pages = "77--87",

journal = "Cancer Cell",

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T1 - STAT1 acts as a tumor promoter for leukemia development

AU - Kovacic, Boris

AU - Stoiber, Dagmar

AU - Moriggl, Richard

AU - Weisz, Eva

AU - Ott, René G

AU - Kreibich, Rita

AU - Levy, David E

AU - Beug, Hartmut

AU - Freissmuth, Michael

AU - Sexl, Veronika

PY - 2006/7

Y1 - 2006/7

N2 - The tumor suppressor STAT1 is considered a key regulator of the surveillance of developing tumors. Here, we describe an unexpected tumor-promoting role for STAT1 in leukemia. STAT1(-/-) mice are partially protected from leukemia development, and STAT1(-/-) tumor cells induce leukemia in RAG2(-/-) and immunocompetent mice with increased latency. The low MHC class I protein levels of STAT1(-/-) tumor cells enable efficient NK cell lysis and account for the enhanced tumor clearance. Strikingly, STAT1(-/-) tumor cells acquire increased MHC class I expression upon leukemia progression. These findings define STAT1 as a tumor promoter in leukemia development. Furthermore, we describe the upregulation of MHC class I expression as a general mechanism that allows for the escape of hematopoietic malignancies from immune surveillance.

AB - The tumor suppressor STAT1 is considered a key regulator of the surveillance of developing tumors. Here, we describe an unexpected tumor-promoting role for STAT1 in leukemia. STAT1(-/-) mice are partially protected from leukemia development, and STAT1(-/-) tumor cells induce leukemia in RAG2(-/-) and immunocompetent mice with increased latency. The low MHC class I protein levels of STAT1(-/-) tumor cells enable efficient NK cell lysis and account for the enhanced tumor clearance. Strikingly, STAT1(-/-) tumor cells acquire increased MHC class I expression upon leukemia progression. These findings define STAT1 as a tumor promoter in leukemia development. Furthermore, we describe the upregulation of MHC class I expression as a general mechanism that allows for the escape of hematopoietic malignancies from immune surveillance.

KW - Animals

KW - B-Lymphocytes/metabolism

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Cell Survival/genetics

KW - Cell Transformation, Neoplastic/genetics

KW - DNA-Binding Proteins/genetics

KW - Disease Progression

KW - Genotype

KW - Histocompatibility Antigens Class I/immunology

KW - Interferon-gamma/genetics

KW - Killer Cells, Natural/immunology

KW - Leukemia, Experimental/genetics

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Oncogene Proteins v-abl/genetics

KW - Oncogene Proteins, Fusion/genetics

KW - Phenotype

KW - STAT1 Transcription Factor/deficiency

KW - Stem Cells/metabolism

KW - Survival Analysis

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U2 - 10.1016/j.ccr.2006.05.025

DO - 10.1016/j.ccr.2006.05.025

M3 - Journal article

C2 - 16843267

SN - 1535-6108

VL - 10

SP - 77

EP - 87

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

STAT1 acts as a tumor promoter for leukemia development

Abstract

Keywords

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