UCLA researchers in the Department of Obstetrics and Gynecology at the David Geffen School of Medicine have developed a new mouse model for Wnt signaling related to triple negative breast cancer.
BACKGROUND:
Approximately 250,000 people in the US are diagnosed with breast cancer annually. Breast cancer can be separated into different subtypes that are generally diagnosed based upon the presence, or lack of, three receptors known to propagate most breast cancers: estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2. The most successful treatments for breast cancer target these receptors. Unfortunately, none of these receptors are present in women with triple negative breast cancer (TNBC), and therefore resistant to highly effective receptor targeted therapies. Depending on the stage of its diagnosis, TNBC can be particularly aggressive, and more likely to recur than other subtypes of breast cancer. Efforts are currently underway to characterize these TNBC cancers at a molecular level and develop novel systems and strategies for new therapeutics.
INNOVATION:
UCLA researchers led by Prof. Gustavo A Miranda-Carboni have developed a novel mouse model for TNBC. They have demonstrated that the overexpression of an early Wnt signaling protein, which regulates maintenance of mammary gland stem cells, mimics human TNBCs, and express human relevant markers. Furthermore, this model is validated by use of a known inhibitor of stem cell renewal and proliferation. This demonstrates that the system is useful in testing and discovering novel therapeutics for human TNBCs.
POTENTIAL APPLICATIONS:
• A useful tool in validating, discovering, and characterizing novel therapeutics in a mouse model for human TNBC
ADVANTAGES:
• Cells mimic/display human relevant TNBC markers such as HMGA2, EZH2 ,WNT10B, βCATEIN CD44 and CD24.
• Can track cancer initiating stem cells and test response to new therapeutics in the mammary gland.
• Can observe loss of cancer proliferation markers and restoration of tumor suppressor genes in this model of TNBC, and its response to potential therapeutics.
DEVELOPMENT-TO-DATE:
Researchers have validated their mouse model of TNBC with a small molecule inhibitor for other cancer types. Cancer cells display human relevant markets.
RELATED PAPERS:The WNT10B Network Is Associated with Survival and Metastases in Chemoresistant Triple-Negative Breast Cancer, Cancer Res. 2019 Mar 1;79(5):982-993. PMID: 23307470.
WNT10B/β-catenin signalling induces HMGA2 and proliferation in metastatic triple-negative breast cancer, EMBO Mol Med. 2013 Feb;5(2):264-79. PMID: 23307470.
The natural compound Jatrophone interferes with Wnt/β-catenin signaling and inhibits proliferation and EMT in human triple-negative breast cancer, PLoS One. 2017 Dec 27;12(12):e0189864. PMID: 29281678.