Cancer stem cell heterogeneity in hereditary breast cancer.

The cancer stem cell hypothesis proposes that tumors arise in stem or progenitor cells generating in tumors driven by a subcomponent that retains cancer stem cell properties. Recent evidence supports the hypothesis that the BRCA1 gene involved in hereditary breast cancer plays a role in breast stem cell function. Furthermore, studies using mouse BRCA1 knockout models provide evidence for the existence of heterogeneous cancer stem cell populations in tumors generated in these mice. Although these populations may arise from different stem/progenitor cells, they share the expression of a common set of stem cell regulatory genes and show similar characteristics in in vitro mammosphere assays and xenograft models. Furthermore, these 'cancer stem cells' display resistance to chemotherapeutic agents. These studies suggest that breast tumors may display intertumor stem cell heterogeneity. Despite this heterogeneity, cancer stem cells may share common characteristics that can be used for their identification and for therapeutic targeting.