İnsan meme kanseri hücre hatlarında ve meme tümörlerinde notch yolağı reseptör ve ligandlarının ekspresyonu

ABSTRACTExpression of Notch Signaling Pathway Receptors and Ligands inHuman Breast Cancer Cell Lines and Human Breast TumorsÖzden YalçınM.Sc. in Molecular Biology and GeneticsSupervisor: Prof. Dr. Mehmet ÖZTÜRKSeptember 2004, 69 pagesBreast cancer is the most common cancer type in women. Traditional therapiestargeting proliferating cells cannot be effective in all cases and recursion is observedin 40% of breast cancers within 10 years. One possible explanation is that the originof breast cancer is `breast cancer stem cells?, which cannot be killed by thesetherapies. Cancer stem cells are thought to be formed due to deregulation of normalstem cells. Breast tissue also contains normal stem cells required for its developmentduring puberty and pregnancy; and putative breast cancer stem cells have recentlybeen isolated. Investigation of pathways used in stem cell regulation is the first stepto understand the contribution of stem cells to tumorgenesis and design newtherapeutic approaches. Notch signaling is involved in stem cell maintenance andmany types of human cancers. Notch activation in mouse mammary glanddevelopment and tumorigenesis lead us to its possible role in human mammary glandtumorigenesis. The expression of Notch receptors and ligands were identified bysemi-quantitative RT-PCR in human breast cancer cell lines and tumor samples. Itwas found that Notch3 expression was strongly upregulated in cancer cells lines andtumors compared to normal cell line, while other receptors and ligands did not havesignificant changes in expression. Depending on the upregulation of Notch3expression in putative breast stem cells, we may hypothesize that its activation keepscells in a stem cell like phenotype, inhibit differentiation and increase cancer risk.ii