Metastatic Progression of Breast Cancer by Allelic Loss on Chromosome 18q21

摘要

Despite that the level of TGFbeta is increased locally and systemically in advanced breast tumors particularly at the leading edges and in metastasis, the molecular basis of a role of TGFBETA Pin metastatic breast cancer remained elusive. Our studies demonstrate that over-expression of SMAD7 localized to chromosome 18q is frequently observed in breast tumors providing an alternate mechanism for the disruption of Smad signaling pathway in breast cancer. The inactivation of Smad signaling due to overexpression of SMAD7 in cell culture was associated with differential expression of genes that favor epithelial to mesenchymal transition (EMT). We believe that these observations suggest that intact Smad signaling plays a major role in the suppression of breast cancer metastatic phenotype. In the future studies, we are planning to use model cell lines to identify and characterize the mediator and effector genes that regulate metastatic progression of breast cancer upon inactivation of the Smad signaling mediated events.