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Mol. Cells 2011; 31(2): 181-189

Published online December 3, 2010

https://doi.org/10.1007/s10059-011-0020-z

© The Korean Society for Molecular and Cellular Biology

Epigenetic Up-Regulation of Leukemia Inhibitory Factor (LIF) Gene During the Progression to Breast Cancer

Jung Eun Shin1,2, Su Hyung Park1,2, and Yeun Kyu Jang1,2,*

1Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea, 2Yonsei Biomolecule Research Initiative, Yonsei University, Seoul 120-749, Korea

Correspondence to : *Correspondence: ykjang@yonsei.ac.kr

Received: October 18, 2010; Revised: November 10, 2010; Accepted: November 12, 2010

Abstract

The interleukin 6 family of cytokines including leukemia inhibitory factor (LIF) regulates the progression of several types of cancer. However, although LIF overexpression during breast cancer progression was observed in our previous report, the molecular mechanisms responsible for this deregulation remain largely unknown. Here we show that LIF expression is epigenetically up-regulated via DNA demethylation and changes in histone methylation status within its promoter region in the isogenic MCF10 model. Bisulfite sequencing revealed the CpG pairs within the promoter region are hypermethylated in normal breast epithelial cells, but extensively demethylated as breast cancer progresses. In agreement with the DNA methyla-tion pattern, our chromatin immunoprecipitation showed that inactive epigenetic marks such as MeCP2 occupancy and histone H3-Lys9-dimethylation significantly decreased during the progression to breast cancer but an active histone mark was increased in an inverse manner. Also, the occupancy of the transcription factor Sp1, which has higher affinity for hypomethylated CpGs, increased. RNAi-mediated knockdown of LIF expression resulted in a significant reduction of cell growth and colony formation in breast cancer cells, suggesting the potential role of LIF-LIF receptor axis in autocrine stimulation of cancer cells. Collectively, our data suggest that the epigenetic up-regu-lation of the LIF gene likely play an important role in the development of breast cancer.

Keywords DNA methylation, histone methylation, isogenic MCF10 cell lines, leukemia inhibitory factor (LIF), MeCP2

Article

Research Article

Mol. Cells 2011; 31(2): 181-189

Published online February 28, 2011 https://doi.org/10.1007/s10059-011-0020-z

Copyright © The Korean Society for Molecular and Cellular Biology.

Epigenetic Up-Regulation of Leukemia Inhibitory Factor (LIF) Gene During the Progression to Breast Cancer

Jung Eun Shin1,2, Su Hyung Park1,2, and Yeun Kyu Jang1,2,*

1Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea, 2Yonsei Biomolecule Research Initiative, Yonsei University, Seoul 120-749, Korea

Correspondence to:*Correspondence: ykjang@yonsei.ac.kr

Received: October 18, 2010; Revised: November 10, 2010; Accepted: November 12, 2010

Abstract

The interleukin 6 family of cytokines including leukemia inhibitory factor (LIF) regulates the progression of several types of cancer. However, although LIF overexpression during breast cancer progression was observed in our previous report, the molecular mechanisms responsible for this deregulation remain largely unknown. Here we show that LIF expression is epigenetically up-regulated via DNA demethylation and changes in histone methylation status within its promoter region in the isogenic MCF10 model. Bisulfite sequencing revealed the CpG pairs within the promoter region are hypermethylated in normal breast epithelial cells, but extensively demethylated as breast cancer progresses. In agreement with the DNA methyla-tion pattern, our chromatin immunoprecipitation showed that inactive epigenetic marks such as MeCP2 occupancy and histone H3-Lys9-dimethylation significantly decreased during the progression to breast cancer but an active histone mark was increased in an inverse manner. Also, the occupancy of the transcription factor Sp1, which has higher affinity for hypomethylated CpGs, increased. RNAi-mediated knockdown of LIF expression resulted in a significant reduction of cell growth and colony formation in breast cancer cells, suggesting the potential role of LIF-LIF receptor axis in autocrine stimulation of cancer cells. Collectively, our data suggest that the epigenetic up-regu-lation of the LIF gene likely play an important role in the development of breast cancer.

Keywords: DNA methylation, histone methylation, isogenic MCF10 cell lines, leukemia inhibitory factor (LIF), MeCP2

Mol. Cells
Nov 30, 2023 Vol.46 No.11, pp. 655~725
COVER PICTURE
Kim et al. (pp. 710-724) demonstrated that a pathogen-derived Ralstonia pseudosolanacearum type III effector RipL delays flowering time and enhances susceptibility to bacterial infection in Arabidopsis thaliana. Shown is the RipL-expressing Arabidopsis plant, which displays general dampening of the transcriptional program during pathogen infection, grown in long-day conditions.

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