Expression of SOX11 and HER2 and their association with recurrent breast cancer

BACKGROUND: Recurrent breast cancer occurs as a result of divergent gene expression in response to therapeutic intervention. A recent report showed that SOX11, an embryogenic mammary transcription factor, is overexpressed in breast cancer. HER2 is also dysregulated in breast cancer stem cells; however, the relative expression of these two genes in recurrent breast cancer has not been investigated. METHODS: Mouse models of mild and advanced stage recurrent breast cancer were developed via implantation of different doses of 4T1 Luc2GFP cells. The cellular morphology of normal and recurrent breast cancer tissues was analyzed using standard histological methods. SOX11, HER2, and ALDH1 expression levels were analyzed via immunohistochemistry and western blotting. RESULTS: Histological analyses revealed that treatment with doxorubicin limited mild recurrent cancer but was ineffective against advanced stage recurrent cancers, as evidenced by increased cell proliferation. SOX11 was consistently overexpressed in mild and advanced stage breast cancers treated with doxorubicin, relative to HER2, which exhibited reduced expression in response to doxorubicin treatment in both mild and advanced stage recurrent breast cancer. In advanced stage recurrent breast cancer, SOX11 expression was more readily observed across the cell surface and was correlated with the overexpression of the breast cancer stem cell marker ALDH1. CONCLUSIONS: These results show that SOX11 expression was directly associated with breast cancer stem cell populations. In contrast, HER2 expression was strongly associated with drug treatment effects, but was not correlated with breast cancer stem cell survival in recurrent breast cancer.