Browsing by Subject "Breast Cancer."

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Open Access
Expression of notch signaling pathway receptors and ligands in human breast cancer cell lines and human breast tumors
(2004) Yalçın, Özden
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.
Open Access
RNASEL G1385A variant and breast cancer susceptibility
(2003) Sevinç, Akın
RNASEL (MIM# 180435) encodes for the ubiquitously expressed ribonuclease L (RNase L), which mediates the antiviral and pro-apoptotic activities of the 2-5A system. Recently, RNASEL Arg462Gln (G1385A) variant is shown to be implicated in up to 13% of prostate cancer cases. Furthermore, RNASEL mutations segregating with disease within hereditary prostate cancer (HPC) families, and loss of heterozygosity (LOH) in tumor tissues have been reported. RNase L has been proposed to suppress the development of cancer through its ability to degrade RNA and initiate a cellular stress that leads to apoptosis. Analysis for allelic losses at the long arm of the chromosome 1 suggested that inactivation of a gene(s) on 1q23-32, which encompasses the RNASEL locus, might contribute to the genesis of breast cancer. Based on chromosomal location and function of RNASEL, and pleitropic effects of cancer associated mutations, we south to investigate the hypothesis that Arg462Gln variant of RNASEL is associated with breast cancer risk. The homozygote mutant (odds ratio (OR) = 0.75, 95% CI= 0.49- 1.14), heterozygote (OR=1.02, 95% CI= 0.76-1.37), or the genotype having at least one mutant allele (OR= 0.94, 95% CI=0.72-1.24) was found to be not associated with the breast cancer risk. The adjustment of the data with age, menopausal, smoking status, body-mass-index, age at menarche, age of 1st pregnancy, number of children, and family history of breast cancer did not change the results (homozygote mutant (OR= 0.72, 95% CI= 0.46-1.12), heterozygote (OR= 0.95, 95% CI= 0.70-1.29), or genotype having at least one mutant allele (OR= 0.89, 95% CI= 0.66-1.18)). In conclusion, our study reports no association between the RNASEL G1385A variant and breast cancer risk.
Open Access
Stem cell-like protein expression in breast cancer cell lines
(2003) Sever, Nurettin İlter
Breast cancer is the most common type of cancer and the second leading cause of cancer deaths among women. Most of breast carcinoma arises from the breast ductal epithelium. Recent studies in the past decade have displayed that many organs in our body possess organ-specific stem cells which have the capacity of self-renewal and differentiation toward specialized cell types which are specific for that organ. Breast is also one of these organs and breast epithelium contains stem/progenitor cells which give rise to two types of differentiated breast epithelial cell types: luminal epithelial and myoepithelial. Due to their property of division-competence for selfrenewal, stem cells are more prone to malignant transformation than more differentiated cell types. Therefore, it is considered that breast cancer may have arisen from a stem/progenitor cell found in mammary epithelium and recent studies support this hypothesis. In the study described in this thesis, breast cancer cell lines have been demonstrated to display stem/progenitor cell-like protein expression. Breast cancer cell lines have been characterized according to their marker protein expression related to the differentiation status of the mammary epithelial cell type by using immunofluorescence and Western blotting techniques. Also, single cellcloning of GI-101 cell line has been performed. It has been demonstrated that a single cell could give rise to different cell populations, further supporting the hypothesis that breast cancer cell lines display stem/progenitor cell-like protein expression.