Estrogen-regulated extracellular matrix remodeling genes in MCF-7 breast cancer cells

• Identification of estrogen‐regulated ECM remodeling genes (ECMRGs) was attempted.
• 189 estrogen‐regulated ECMRGs were identified in MCF-7 cells.
• These include ECM remodeling enzymes, their inhibitors, and ECM structural proteins.
• MCF-7 and MDA-MB-231 cells differentially expressed estrogen‐regulated ECMRGs.
• Results suggest an important role for estrogen in tumor cell mediated ECM remodeling.

The involvement of estrogen in breast tumorigenesis is well established. However, its role in extracellular matrix (ECM) remodeling, which is crucial to invasion and metastasis of breast tumors, is not completely understood. In this context, knowledge of the complete repertoire of estrogen-regulated ECM remodeling genes (ECMRGs) can be of great value. To identify the estrogen-regulated ECMRGs, we analyzed our published gene expression microarray data of control and estrogen treated ER-positive MCF-7 breast cancer cells. Here we show that out of 3411 genes regulated by estrogen, 189 were ECMRGs. These include proteases (MMPs, ADAMTSs and cathepsins), their endogenous inhibitors (TIMPs, cystatins) and ECM structural proteins. Eight ECMRGs selected randomly, showed differential expression in MCF-7 (non-invasive) and MDA-MB-231 (highly invasive) cells. Notably, estrogen stimulation of MCF-7 cells altered the expression of these ECMRGs in a manner that closely mimicked their expression in MDA-MB-231 cells. These data not only support the notion of estrogenic control of ECM remodeling in the breast, but also implicate ECMRGs in invasion and metastasis.