Identification of Black Cohosh-Regulated Markers in Mammary Tumors from MMTV-neu Mice

Defense Date


Graduation Date

Fall 1-1-2007


Campus Only

Submission Type


Degree Name





School of Pharmacy

Committee Chair

Vicki L. Davis

Committee Member

Kyle W. Selcer

Committee Member

Wilson S. Meng


biomarkers, black cohosh, breast cancer, cimicifuga racemosa, herbal supplement, metastasis


Black cohosh is an herbal supplement used by women to control the symptoms of menopause, mainly hot flashes. While many view black cohosh as a safe alternative to hormone replacement therapy, there is limited research regarding the effects of black cohosh on breast tumor development and progression. Previous work in our laboratory has shown that black cohosh treatment did not alter primary mammary tumor incidence and latency in MMTV/neu transgenic mice, but did significantly increase the incidence of metastatic cancer. To identify potential markers of black cohosh's influence on tumor metastasis, primary mammary tumors from control and black cohosh-treated neu mice were analyzed for changes in protein and/or gene expression for the following factors related to cancer progression: matrix metalloproteinases 2 and 9, vascular endothelial growth factor, cyclooxygenase-2 (COX-2), and ATP1a2 - the α2 subunit of the Na+/K+-ATPase enzyme. A significant increase (p = 0.005) was found in atp1a2 gene expression in primary tumors from black cohosh-treated animals with gross metastatic lesions compared to control animals with the same degree of metastasis. COX-2 gene expression was significantly lower in the same group (p = 0.019). Expression of the atp1a2 and COX-2 genes were found to be modified by black cohosh treatment in primary mammary tumors from MMTV-neu mice. These genes may have importance as markers and could be used to determine if black cohosh elicits similar effects on marker expression in human breast tumors. If future studies show black cohosh alters marker expression in humans as it did in MMTV-neu mice, then this mouse model may be an appropriate predictor of black cohosh's action in women, suggesting black cohosh may increase the risk of human breast cancer metastasis.





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