Expression of notch signaling pathway receptors and ligands in human breast cancer cell lines and human breast tumors

Abstract

Breast cancer is the most common cancer type in women. Traditional therapies targeting proliferating cells cannot be effective in all cases and recursion is observed in 40% of breast cancers within 10 years. One possible explanation is that the origin of breast cancer is ‘breast cancer stem cells’, which cannot be killed by these therapies. Cancer stem cells are thought to be formed due to deregulation of normal stem cells. Breast tissue also contains normal stem cells required for its development during puberty and pregnancy; and putative breast cancer stem cells have recently been isolated. Investigation of pathways used in stem cell regulation is the first step to understand the contribution of stem cells to tumorgenesis and design new therapeutic approaches. Notch signaling is involved in stem cell maintenance and many types of human cancers. Notch activation in mouse mammary gland development and tumorigenesis lead us to its possible role in human mammary gland tumorigenesis. The expression of Notch receptors and ligands were identified by semi-quantitative RT-PCR in human breast cancer cell lines and tumor samples. It was found that Notch3 expression was strongly upregulated in cancer cells lines and tumors compared to normal cell line, while other receptors and ligands did not have significant changes in expression. Depending on the upregulation of Notch3 expression in putative breast stem cells, we may hypothesize that its activation keeps cells in a stem cell like phenotype, inhibit differentiation and increase cancer risk.