Epigenetic Reversion of Breast Cancer DNA
Using breast cancer cells, researchers have demonstrated that cancer phenotype can be reversibly altered by manipulations other than genetic means. Breast cancer cells grown in 3-D culture can be induced to form normal breast duct-like structures, as opposed to dense cell masses, by activating or inhibiting specific signaling pathways, including antibody binding to the extracellular matrix protein fibronectin.
In addition, cancer cell DNA, which has been shown previously to resist enzymatic digestion, could be rendered accessible to enzyme digestion following reversion of its 3-D growth phenotype. Importantly, such reversion of breast cancer cells could be overturned by removing the reversion stimuli, resulting in a return to cancerous growth and resistance to enzymatic DNA digestion.
These data underscore the plasticity displayed by cancer cells: even after a cell adopts a cancerous phenotype, it can be manipulated to regain "normal" 3-D structure, growth, and DNA organization (ie, enzyme accessibility). The intimate link between cellular growth phenotype and susceptibility to enzymatic DNA digestion suggests that analysis of DNA accessibility may have future diagnostic implications.
Sandal T, Valyi-Nagy K, Spencer VA, Folberg R, Bissell MJ, Maniotis AJ. Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in DNA sequestration as measured by AluI restriction enzyme. Am J Pathol 2007 170:1739