Department of Paediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Laboratory of Cancer Epigenetics, Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, India.
Adv Exp Med Biol. 2019;1152:293-310. doi: 10.1007/978-3-030-20301-6_16.
Epigenetics refers to alterations in gene expression due to differential histone modifications and DNA methylation at promoter sites of genes. Epigenetic alterations are reversible and are heritable during somatic cell division, but do not involve changes in nucleotide sequence. Epigenetic regulation plays a critical role in normal growth and embryonic development by controlling transcriptional activities of several genes. In last two decades, these modifications have been well recognized to be involved in tumor initiation and progression, which has motivated many investigators to incorporate this novel field in cancer drug development. Recently, growing number of epigenetic changes have been reported that are involved in the regulations of genes involved in breast tumor growth and metastasis. Drugs possessing epigenetic modulatory activities known as epi-drugs, mainly the inhibitors of histone deacetylases (HDACs) and DNA methyltransferases (DNMTs). Some of these drugs are undergoing different clinical trials for breast cancer treatment. Several phytochemicals such as green tea polyphenols, curcumin, genistein, resveratrol and sulforaphane have also been shown to alter epigenetic modifications in multiple cancer types including breast cancer. In this chapter, we summarize the role of epigenetic changes in breast cancer progression and metastasis. We have also discussed about various epigenetic modulators possessing chemopreventive and therapeutic efficacy against breast cancer with future perspectives.
表观遗传学是指由于组蛋白修饰和基因启动子区域 DNA 甲基化的差异导致的基因表达改变。表观遗传改变是可逆的，并且在体细胞分裂过程中是可遗传的，但不涉及核苷酸序列的变化。表观遗传调控通过控制几个基因的转录活性，在正常生长和胚胎发育中起着关键作用。在过去的二十年中，这些修饰已被充分认识到参与肿瘤的起始和进展，这促使许多研究人员将这一新领域纳入癌症药物开发。最近，越来越多的表观遗传变化被报道涉及参与乳腺癌生长和转移的基因调节。具有表观遗传调节活性的药物被称为 epi 药物，主要是组蛋白去乙酰化酶（HDACs）和 DNA 甲基转移酶（DNMTs）抑制剂。其中一些药物正在进行不同的临床试验，用于治疗乳腺癌。一些植物化学物质，如绿茶多酚、姜黄素、染料木黄酮、白藜芦醇和萝卜硫素，也被证明可以改变多种癌症类型，包括乳腺癌中的表观遗传修饰。在本章中，我们总结了表观遗传变化在乳腺癌进展和转移中的作用。我们还讨论了各种具有化学预防和治疗乳腺癌功效的表观遗传调节剂，并对其未来前景进行了展望。
