Deregulation of the beta-catenin pathway leads to several types of tumors including colon, skin cancer, and leukemia. In these tissues, beta-catenin regulates the production of stem/progenitor cells. Loss of negative regulators of the pathway, amplification of several positive regulators, and upregulation of beta-catenin, occur in breast cancer. Our laboratory has generated a transgenic mouse that expresses an activated form of beta-catenin. These mice develop mammary adenocarcinomas at 4.5 months that are preceded by precocious alveolar development, suggesting a connection between pathways controlling normal alveologenesis and predisposition to breast cancer. Recent evidence has shown that breast cancer arises from cancer stem cells. The possibility that breast cancer stem cells derive from normal stem/progenitors is supported by observations that breast cancer has long latency, is often slow growing, and appears decades after exposure to the primary insult. This proposal will use our beta-catenin mouse model and a second mouse that permits detection of beta-catenin signaling to determine the relationship between breast progenitor cell expansion and predisposition to breast cancer.
| Teissedre, Brigitte; Pinderhughes, Alicia; Incassati, Angela et al. (2009) MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors. PLoS One 4:e4537 |
