IMR Press / FBL / Volume 14 / Issue 8 / DOI: 10.2741/3425

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
The dark and the bright side of Stat3: proto-oncogene and tumor-suppressor
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1 Institute of Molecular Pathology (IMP), Austria
2 Institute of Pharmacology, Medical University of Vienna (MUW), Austria
3 Ludwig-Boltzmann-Institute for Cancer Research (LBI-CR), Austria
4 Institute of Clinical Pathology, Medical University of Vienna (MUW), Austria
Front. Biosci. (Landmark Ed) 2009, 14(8), 2944–2958; https://doi.org/10.2741/3425
Published: 1 January 2009
Abstract

Stat transcription factors have been implicated in tumorigenesis in mice and men. Stat3 and Stat5 are considered powerful proto-oncogenes, whereas Stat1 has been demonstrated to suppress tumor formation. We demonstrate here for the first time that a constitutive active version of Stat3alpha (Stat3alphaC) may also suppress transformation. Mouse embryonic fibroblasts (MEFs) deficient for p53 can be transformed with either c-myc or with rasV12 alone. Interestingly, transformation by c-myc is efficiently suppressed by co-expression of Stat3alphaC, but Stat3alphaC does not interfere with transformation by the rasV12-oncogene. In contrast, transplantation of bone marrow cells expressing Stat3alphaC induces the formation of a highly aggressive T cell leukemia in mice. The leukemic cells invaded multiple organs including lung, heart, salivary glands, liver and kidney. Interestingly, transplanted mice developed a similar leukemia when the bone marrow cells were transduced with Stat3beta, which is also constitutively active when expressed at significant levels. Our experiments demonstrate that Stat3 has both – tumor suppressing and tumor promoting properties.

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