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

摘要

Genetic and epigenetic inactivation of SMAD4 are rare occurrences in breast tumors despite it is localized to chromosome 18q and serves as a frequent target for inactivation in advanced gastrointestinal cancers. On the other hand, our studies demonstrated that SMAD8 could be an alternate target gene which undergoes epigenetic silencing of gene expression in nearly 30% of breast cancers. These studies provided the first line of evidence for an alternate mechanism for disruption of the Smad signaling events in breast cancer. Smad8 is an R-Smad involved in the regulation of BMP-responsive genes including those affect bone metabolism. Since bone metastasis is frequently associated with breast cancer, it is likely that Smad8 inactivation in breast cancer could play a role in metastasis/ bone metastasis. In the future, we are planning to follow up these critical observations and use model cell lines and mouse models to identify and characterize the mediator and effector genes that regulate metastatic progression of breast cancer due to Smad8 inactivation.