Tuberc Respir Dis > Volume 70(3); 2011 > Article
Tuberculosis and Respiratory Diseases 2011;70(3):206-217.
DOI: https://doi.org/10.4046/trd.2011.70.3.206    Published online March 1, 2011.
The Regulation of FOXP3 Expression by the Treatment of TGF-beta and the Modification of DNA Methylation in Lung Cancer Cell Lines.
Sang Won Um, Sang Hee Lee, Hojoong Kim, O Jung Kwon, Hangrae Kim, Jae Seung Kang, Wang Jae Lee
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. sangwonum@skku.edu
2Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Abstract
BACKGROUND
Transcription factor FOXP3 characterizes the thymically derived regulatory T cells. FOXP3 is expressed by cancer cell itself and FOXP3 expression was induced by TGF-beta treatment in pancreatic cancer cell line. However, the expression of FOXP3 expression is not well known in patients with lung cancer. This study was conducted to investigate the expression of FOXP3 in patients with lung cancer and to investigate the regulation of FOXP3 expression by the treatment of TGF-beta and DNA methyltransferase inhibitor in lung cancer cell lines. METHODS: FOXP3 expression in the tissue of patients with resected non-small cell lung cancer (NSCLC) was evaluated by immunohistochemistry. The regulation of FOXP3 expression was investigated by Western blot and RT-PCR after lung cancer cell lines were stimulated with TGF-beta1 and TGF-beta2. The regulation of FOXP3 expression was also investigated by RT-PCR and flow cytometry after lung cancer cell lines were treated with DNA methyltransferase inhibitor (5-AZA-dC). RESULTS: FOXP3 expression was confirmed in 27% of patients with NSCLC. In NCI-H460 cell line, TGF-beta2 decreased FOXP3 mRNA and protein expressions. In A549 cell line, both TGF-beta1 and TGF-beta2 decreased FOXP3 mRNA and protein expressions. 5-AZA-dC increased FOXP3 mRNA expression in NCI-H460 and A549 cell lines. Moreover, 5-AZA-dC increased intracellular FOXP3 protein expression in A549 cell lines. CONCLUSION: It was shown that FOXP3 is expressed by cancer cell itself in patients with NSCLC. Treatment of TGF-beta2 and DNA methyltransferase inhibitor seems to be associated with the regulation of FOXP3 expression in lung cancer cell lines.
Key Words: Lung Neoplasms, FOXP3 protein, human, Transforming Growth Factor beta, DNA Methylation


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