Enhanced T Cell Lymphoma in NOD.Stat5b Transgenic Mice Is Caused by Hyperactivation of Stat5b in CD8+ Thymocytes

Bo Chen, Bing Yi, Rui Mao, Haitao Liu, Jinhua Wang, Ashok Kumar Sharma, Stephen Peiper, Warren J. Leonard, Jin-Xiong She

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Activation of signal transducers and activators of transcription (STAT) proteins may be critical to their oncogenic functions as demonstrated by the development of B-cell lymphoma/leukemia in transgenic (TG) mice overexpressing a constitutively activated form of Stat5b. However, low incidence of CD8+ T cell lymphoma was observed in B6 transgenic mice overexpressing a wild-type Stat5b (B6.Stat5bTg) despite of undetectable Stat5b phosphorylation and the rate of lymphomagenesis was markedly enhanced by immunization or the introduction of TCR transgenes [1]. Here, we report that the wild-type Stat5b transgene leads to the acceleration and high incidence (74%) of CD8+ T cell lymphoblastic lymphomas in the non-obese-diabetic (NOD) background. In contrast to the B6.Stat5bTg mice, Stat5b in transgenic NOD (NOD.Stat5bTg) mice is selectively and progressively phosphorylated in CD8+ thymocytes. Stat5 phosphorylation also leads to up-regulation of many genes putatively relevant to tumorigenesis. Treatment of NOD.Stat5bTg mice with cancer chemopreventive agents Apigenin and Xanthohumol efficiently blocked lymphomagenesis through reduction of Stat5 phosphorylation and genes up-regulated in the NOD.Stat5bTg mice. These results suggest that NOD genetic background is critical to the Stat5b-mediated lymphomagenesis through regulation of Stat5 hyperactivation. NOD.Stat5bTg mouse is an excellent model for studying the molecular mechanisms underlying lymphomagenesis and testing novel chemoprevention strategies.

Original languageEnglish (US)
Article numbere56600
JournalPloS one
Volume8
Issue number2
DOIs
StatePublished - Feb 14 2013

Fingerprint

Phosphorylation
thymocytes
T-cells
T-Cell Lymphoma
Thymocytes
lymphoma
Transgenic Mice
T-lymphocytes
genetically modified organisms
mice
Genes
Transgenes
STAT Transcription Factors
Immunization
Apigenin
phosphorylation
B-Cell Leukemia
Inbred NOD Mouse
Molecular Models
Incidence

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Enhanced T Cell Lymphoma in NOD.Stat5b Transgenic Mice Is Caused by Hyperactivation of Stat5b in CD8+ Thymocytes. / Chen, Bo; Yi, Bing; Mao, Rui; Liu, Haitao; Wang, Jinhua; Sharma, Ashok Kumar; Peiper, Stephen; Leonard, Warren J.; She, Jin-Xiong.

In: PloS one, Vol. 8, No. 2, e56600, 14.02.2013.

Research output: Contribution to journalArticle

Chen, Bo ; Yi, Bing ; Mao, Rui ; Liu, Haitao ; Wang, Jinhua ; Sharma, Ashok Kumar ; Peiper, Stephen ; Leonard, Warren J. ; She, Jin-Xiong. / Enhanced T Cell Lymphoma in NOD.Stat5b Transgenic Mice Is Caused by Hyperactivation of Stat5b in CD8+ Thymocytes. In: PloS one. 2013 ; Vol. 8, No. 2.
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