Induction of HOXA9 expression in three-dimensional organotypic culture of the Claudin-low breast cancer cells
Metrics: PDF 1760 views | HTML 2084 views | ?
Miao Li1, Xi Li2, Yan Zhuang3, Yan Wang4, Matthew E. Burow3, Bridgette Collins-Burow3, Min Xue5, Chengjie Song5, Bin Shan6
1Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China
2Department of Sports Medicine and Joint Surgery, The People’s Hospital of Liaoning Province, Shenyang, China
3Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA
4Department of Biological Engineering, Zunyi Medical College Zhuhai Campus, Zhuhai, China
5Department of Physiology, Xuzhou Medical College, Xuzhou, China
6Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University Spokane, Spokane, WA, USA
Miao Li, email: [email protected]
Bin Shan, email: [email protected]
Keywords: breast cancer, extracellular matrix, three-dimensional organotypic culture, gene expression, homeobox gene
Received: February 05, 2016 Accepted: June 29, 2016 Published: July 08, 2016
The gene expression signatures of the molecular intrinsic subtypes of breast cancer are regulated by epigenetic mechanisms such as methylation of CpG islands in gene promoters. Epigenetic codes can be regulated by the tumor microenvironment. The Claudin-low subtype is associated with triple-negative invasive ductal carcinomas in patients. Herein we explored epigenetic regulation of gene expression in the Claudin-low breast cancer cells by extracellular matrix (ECM), a key component of the tumor microenvironment. We modeled attachment to ECM using laminin rich ECM three-dimensional organotypic culture (lrECM 3D). In 2D and lrECM 3D cultures we examined expression of the homeobox (HOX) genes that epigenetically regulated in development and cancer. We demonstrated induction of the selected HOX genes in lrECM 3D culture of the Claudin-low breast cancer cells MDA-MB-231 and Hs578T. In particular activation of HOXA9 expression in lrECM 3D culture required binding of bromodomain containing 4 to the HOXA9 promoter and involved CpG hypomethylation. Our findings warrant further investigation of the ECM-regulated epigenetic coding of gene expression in the Claudin-low breast cancer.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.