WNT, Hedgehog and NOTCH signaling pathways in triple negative breast cancer with high and low content of cancer stem cells

Abstract

Background: Triple negative breast cancer is at the greatest interest for the study. Cells of this type of breast cancer do not have receptors for steroid hormones or tyrosine kin-ases. For successful treatment of triple negative cases additional points of application are needed. Such targets could be cancer stem cells. For these types of cells, as well as for other stem cells, there are three main cascades are typical-WNT, Hedgehog and NOTCH. However, the conducted studies indicate the existence of other signaling mechanisms of regulation. In our work, we investigated the expression of the NF-kB, PI3K signaling pathways, as well as WNT, Hedgehog, NOTCH in cells of triple negative breast cancer with high and low content of cancer stem cells (ALDH1A1 level). Methods: The material of 54 cases of infiltrative breast cancer was used. To determine the presence of stem cells in tumor population, the presence of ALDH1A1 protein in cancer cells was investigated. Expression of steroid hormone receptors, HER-2 and Ki-67 was studied by immunohistochemical method to identify cases of triple negative breast cancer. The expression of signaling molecules PI3K, NF-kB, WNT, Notch, Hedgehog was also explored by innunohistochemical method. Results: All cases were investigated for ALDH1A1 expression and were divided into two groups-with low (expression of ALDH1A1 was estimated as 0 and 1þ) and high (expression of ALDH1A1 was estimated as 2þ and 3þ) content of cancer stem cells. It was found that 20% of cases of triple negative breast cancer are positive for ALDH1A1.