Research in our laboratory focuses on understanding the molecular mechanisms that underlie the development and growth of breast cancer, using a combination of cell biology, molecular biology and whole animal approaches. An important component of our program is the identification and evaluation of molecular targets for chemoprevention or treatment of human breast cancer.
Wnt signaling and breast cancer.& Wnt genes were originally identified as mammary oncogenes, and are now recognised to contribute to multiple developmental processes including patterning and differentiation. The Wnt/beta-catenin pathway is activated in many human cancers, including ~95 percent of human colorectal cancers. Thus, one goal of our research is to identify Wnt-responsive genes, and thereby increase our understanding of the molecular basis of human cancer. Wnt target genes identified in the lab include COX-2, PEA3 and Twist. Ongoing studies are designed to understand the role of Wnt/beta-catenin signaling in human breast cancer.&
COX-2 and breast cancer prevention.& COX-2 has attracted considerable attention as a target for both prevention and treatment of cancer: selective COX-2 inhibitors reduce colorectal neoplasia in humans and experimental tumor formation in animal models. We have shown that COX-2 is upregulated by mammary oncogenes in cell lines and breast cancers. Strikingly, knocking out the COX-2 gene or administering a selective COX-2 inhibitor protects against breast cancer in mouse models. Currently, we are examining alternative approaches to suppressing COX/prostaglandin signaling that may effectively suppress cancer without cardiovascular toxicity.
PEA3 factors are key transcriptional regulators.& PEA3 transcription factors are highly expressed in breast and colorectal cancers. Interestingly, we have found that PEA3 factors can transcriptionally activate several Wnt target genes, including both COX-2 and Twist. We speculate that PEA3 factors may play a central role in the upregulation of multiple genes during breast and colorectal neoplasia. Continuing investigations by our laboratory are designed to test this hypothesis.&
Keywords:& Wnt, breast cancer, oncogenic signaling, PEA3, COX-2, Twist, chemoprevention&