The role of chromatin, microRNAs, and tumor stem cells in ovarian cancer

被引:14
作者
Balch, Curtis [3 ]
Nephew, Kenneth P. [1 ,2 ,3 ]
机构
[1] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Med Sci Program, Bloomington, IN 47408 USA
[2] Indiana Univ Sch Med, Dept Med, Dept Obstet & Gynecol, Bloomington, IN 47408 USA
[3] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA
基金
美国国家卫生研究院;
关键词
HISTONE DEACETYLASE INHIBITORS; EPITHELIAL-MESENCHYMAL TRANSITION; DNA METHYLTRANSFERASE 1; TISSUE-GROWTH-FACTOR; SUPPRESSOR GENES; PROMOTER HYPERMETHYLATION; CHEMOTHERAPY RESISTANCE; EPIGENETIC REGULATION; TRANSCRIPTION FACTOR; INTEGRATED ANALYSIS;
D O I
10.3233/CBM-2011-0214
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The term "epigenetics" refers to DNA sequence-independent events that regulate gene expression, including DNA methylation, modifications to histone proteins, and microRNA-associated post-transcriptional control of protein translation. Epigenetic aberrations are now considered a defining characteristic of numerous human pathologies, including cancer. However, in contrast to DNA sequence mutations, many oncogenic epigenetic modifications are potentially reversible, with studies now showing numerous tumor cell types to possess remarkable phenotypic "plasticity," strongly supporting possible reversion of their malignant status. The "epigenome" of one such malignancy, ovarian cancer, has now been studied in depth, with specific epigenetic alterations correlated with tumor initiation, progression, metastasis, and therapy resistance. Ovarian cancer is the most lethal malignancy of the female reproductive tract, largely due to lack or diagnoses of early-stage disease and the eventual develoment of drug resistance; thus, reliable early detection biomarkers and alternative therapies are urgently needed. In this chapter, we discuss the epigenetics of ovarian cancer, including its likely role in the establishment of "cancer stem cells," i.e., highly tumorigenic progenitor cells believed to be largely or solely responsible for the propagation of malignant, chemotherapy-resistant and metastatic disease. Improved understanding of these gene-regulatory phenomena could likely result in improved detection and survival of this highly destructive malignancy.
引用
收藏
页码:203 / 221
页数:19
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