Tumor suppressor and T-regulatory functions of Foxp3 are mediated through separate signaling pathways

Heinze,Emil; Chan,Grace; Mory,Rachel; Khavari,Raz; Alavi,Asif; Chung,Sue  Y.; Nishimura,Robert  N.; Weisbart,Richard  H.

doi:10.3892/ol.2011.307

Tumor suppressor and T-regulatory functions of Foxp3 are mediated through separate signaling pathways

Authors:
- Emil Heinze
- Grace Chan
- Rachel Mory
- Raz Khavari
- Asif Alavi
- Sue Y. Chung
- Robert N. Nishimura
- Richard H. Weisbart
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Affiliations: Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, USA, Department of Research, Veterans Affairs Greater Los Angeles Healthcare System (111S), North Hills, CA 91343, USA, Department of Neurology, University of California, Los Angeles, CA 90095, USA, Department of Research, Veterans Affairs Greater Los Angeles Healthcare System (111S), North Hills, CA 91343, USA
Published online on: May 13, 2011 https://doi.org/10.3892/ol.2011.307
Pages: 665-668

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Abstract

Foxp3 is a nuclear transcription factor that is both a tumor suppressor factor and regulator of T-regulatory cell (Treg) function, and is a potential therapeutic target in both autoimmunity and cancer. In order to distinguish molecular pathways responsible for these separate Foxp3 functions, deletion mutants of Foxp3 proteins were transduced and analyzed for cytotoxic activity in human cancer cell lines Skov3, MDA-MB-231, MCF-7 and Jurkat. Human Foxp3 cDNA mutants were amplified and ligated to produce plasmids for direct cell transfection. Constructs were produced and confirmed by DNA sequencing. Lipofectamine 2000 was used for plasmid transfection. Foxp3 cells were then examined. The results of our experiments reveal retention of tumor suppressor function in the absence of NFAT binding and transcriptional activation required for Treg function. Our results have significant implications for the design of autoimmune and cancer therapies that target Foxp3 and Treg cells.

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