The researchers could alter the Alu I sensitivity of a cell's chromatin by exposing the cell to a single extracellular matrix molecule or by disrupting any of three cytoskeletal systems, which link the outside of the cell to the genome. Using this information, Dr. Maniotis's group developed a new kind of extracellular matrix chip (patent pending) that is being used to study drug-resistance mechanisms to develop new protocols and methods to treat cancer.
Ultimately, the cellular changes that occur during cancer formation affect how the cell interacts with its microenvironment (ECM) and direct changes to the cytoskeleton and finally to the chromatin. Such changes can now be measured directly at the chromatin level. These findings may provide the basis for the design of a new generation of cancer therapeutic agents.
Research was funded by the National Institute of Health and the Department of Energy.
This work involved collaborators at the University of Illinois at Chicago Department of Pathology, the University of Illinois at Chicago Cancer Center, the University of Illinois at Chicago Core Genomics Facility, and the Lawrence Berkeley National Laboratory Life Sciences Division.
Maniotis AJ, Valyi-Nagy K, Karavitis J, Moses J, Boddipali V, Wang Y, Nuñez R, Setty S, Arbieva Z, Bissell MJ, and Folberg R: Chromatin organization measured by Alu I restriction enzyme changes with malignancy and is regulated by the extracellular matrix and the cytoskeleton. Am J Pathol 2005, 166: 1187-1203