A group led by Dr. Peter Lloyd Jones at the University of Dundee, Dundee, Scotland; the University of Colorado Denver, Aurora, CO; and the University of Pennsylvania, Philadelphia, PA has demonstrated that tenascin-C affects proto-oncogene function in breast cancer.
Their report can be found in the February 2010 issue of the American Journal of Pathology.
Breast cancer causes over half a million deaths annually worldwide. Much research has focused on the role of cancer-causing oncogenes and their precursors, non-carcinogenic proto-oncogenes, within the breast epithelium, the tissue from which most breast cancers are derived. The role of the surrounding cells, or stroma, and the molecules they secrete, such as the extracellular matrix, on transformation of proto-oncogenes to oncogenes in breast cancer remains relatively unexplored.
To determine how stromal extracellular matrix remodeling affects proto-oncogene expression in breast epithelia, Taraseviciute et al developed a computational model to quantify changes in a 3-D culture of human mammary epithelial cells. They found that tenascin-C, a stromal glycoprotein whose expression correlates with disease severity, promoted cancer-like properties, similar to the results of overexpression of the oncogene c-met. Indeed, tenascin-C increased c-met expression, and tenascin-C-induced carcinogenesis was inhibited by blocking c-met function. Taken together, these results indicate a role for stromal changes in regulating proto-oncogene function.
Dr. Jones and colleagues suggest "that micro-environmental cues originating within the tumor stroma can act in both a dominant and paracrine fashion to control the expression and function of epithelial genes already associated with the development and progression of breast cancer."
- Taraseviciute A, Vincent BT, Schedin P, Jones PL. Quantitative Analysis of Three-Dimensional Human Mammary Epithelial Tissue Architecture Reveals a Role for Tenascin-C in Regulating c-Met Function. American Journal of Pathology, 2010; 176: 827-838 DOI: 10.2353/ajpath.2010.090006
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