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Epigenetic Changes in Hormonal Related Disease: Uterine Leiomyoma (Fibroids)

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Environmental Epigenetics

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

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Abstract

Epigenetic modifications have been associated with etiology of hormonal related diseases such as breast cancer and prostate cancer. In this chapter, the epigenetic status of a less studied hormonal related disease, uterine leiomyoma, was investigated and its application in potential therapeutic was further discussed. Differential methylation status, the most studied epigenetic signatures, is associated with differential gene expression. Here we investigate whether there are differential epigenetic signatures and their involvement in differential gene expression, apoptosis between two uterine stable cell lines, uterine leiomyoma UtLM-hT (LM) and normal uterine smooth muscle cell lines UtSM-hT (SMC). We first analyzed DNA methylation status using a cancer methylation panel bead array and our data showed that there are differential methylation patterns between the two cell lines. We then selected nine genes with significant differential methylation patterns from the bead array and verified that eight of the nine selected genes show significant differential gene expression between the two cell lines. Additionally, four of the eight genes that demonstrate differential gene expression respond to treatment with a demethylation agent, 5-Aza-2′-deoxycytidine (DAC). Cellular retinol binding protein 1 (CRBP-1) and Tumor necrosis factor super family 10 (TNFSF10) are genes that shows significant differential methylation patterns, gene expression, and responses to DAC between LM and SMC. Altered extracellular matrix (ECM) genes and reduced apoptosis are found in LM and are associated with epigenetic silenced CRBP-1 and TNFSF10 genes.

This chapter showed a systemically investigation from a methylation bead array to explore the possible role of epigenetic changes and their associated biological impacts and potential epigenetic therapy in uterine leiomyoma.

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Acknowledgments

The author thanks Dr. Cruz Velasco for statistical analysis, Dr. Jovanny Zabaleta for technical support, and Ms. Alice LeBlanc for critical proof reading.

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  1. Research Participation Program at Center for Biologics Evaluation and Research at the U.S. Food and Drug Administration, Oak Ridge Institute for Science and Education, Oak Ridge Associate University (ORAU), Oak Ridge, TN, 37831-0117, USA

    Tung-Chin Chiang

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Correspondence to Tung-Chin Chiang .

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  1. Division of Cancer Control and Population Sciences, Epidemiology and Genomic Research Program, Modifiable Risk Factors Branch, National Cancer Institute, Rockville, Maryland, USA

    L. Joseph Su

  2. Research Participation Program at Center for Biologics Evaluation and Research at the U.S. Food and Drug Administration, Oak Ridge Institute for Science and Education, Oak Ridge Associate University (ORAU), Oak Ridge, Tennessee, Tennessee, USA

    Tung-chin Chiang

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Chiang, TC. (2015). Epigenetic Changes in Hormonal Related Disease: Uterine Leiomyoma (Fibroids). In: Su, L., Chiang, Tc. (eds) Environmental Epigenetics. Molecular and Integrative Toxicology. Springer, London. https://doi.org/10.1007/978-1-4471-6678-8_3

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