Suppression of Growth and Transformation of Breast Cancer Stem Cells by Rexinoids

Left Panel: Mammary stem cells are characterized with CD24+/CD49f++/Lin-. Right Panel: Mammary cells from LG100268-treated MMTV-Wnt mice develop much smaller mammospheres compared to vehicle-treated mice.

Our lab is interested in targeting cancer stem cells for the prevention of breast cancer.  Recent research in breast biology supports the cancer stem cell hypothesis, which asserts that malignancies arise in tissue stem cells through dysregulation of processes involved in self-renewal.  This hypothesis carries important implications for the early detection, prevention and treatment of breast cancer.  Previous studies have demonstrated the importance of retinoid signaling in the regulation of self-renewal and differentiation of normal breast stem cells. Furthermore, several molecularly targeted agents, including RXR-selective retinoids (rexinoids), have been shown to prevent the development of estrogen receptor (ER)-negative breast cancer in transgenic mouse models. Bexarotene and LG100268 are two such rexinoids that have been shown to selectively bind RXR receptors.  Based on the effects of these molecularly targeted agents, we hypothesize that rexinoids prevent breast cancer development by suppressing the growth and transformation of the breast stem cell population.  This work is supported by a grant from the Breast Cancer Research Foundation.

Lab members working on this project:  

Jing Zhao, Karrie Wheatley, Ph.D., Jamal Hill, Senior Research Assistant and Yun Zhang, Senior Research Assistant.