title: Enhanced T cell lymphoma in NOD.Stat5b transgenic mice is caused by hyperactivation of Stat5b in CD8+ thymocytes.
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.Stat5b(Tg)) 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.Stat5b(Tg) mice, Stat5b in transgenic NOD (NOD.Stat5b(Tg)) 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.Stat5b(Tg) mice with cancer chemopreventive agents Apigenin and Xanthohumol efficiently blocked lymphomagenesis through reduction of Stat5 phosphorylation and genes up-regulated in the NOD.Stat5b(Tg) mice. These results suggest that NOD genetic background is critical to the Stat5b-mediated lymphomagenesis through regulation of Stat5 hyperactivation. NOD.Stat5b(Tg) mouse is an excellent model for studying the molecular mechanisms underlying lymphomagenesis and testing novel chemoprevention strategies.
authors: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors: Bo
authors: B
authors: Chen
authors: Bing
authors: B
authors: Yi
authors: Rui
authors: R
authors: Mao
authors: Haitao
authors: H
authors: Liu
authors: Jinhua
authors: J
authors: Wang
authors: Ashok
authors: A
authors: Sharma
authors: Stephen
authors: S
authors: Peiper
authors: Warren J
authors: WJ
authors: Leonard
authors: Jin-Xiong
authors: JX
authors: She
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000187:drug effects; D050799:STAT5 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D060168:Thymocytes / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D050799:STAT5 Transcription Factor