Expression of notch signaling pathway receptors and ligands in human breast cancer cell lines and human breast tumors
Author
Yalçın, Özden
Advisor
Öztürk, Mehmet
Date
2004Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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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.