Human Genetics And Molecular Medicine - Master Dissertation

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/104

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Subject: search.filters.subject.Breast Cancer

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    Expression of KIBRA in Breast Cancer Cell Lines
    (Central University of Punjab, 2018) Singh, Garima; Chander,Harish
    Breast cancer the most frequently diagnosed cancer and its metastasis to distant organs accounts the majority of deaths. Numerous genes and proteins are involved in the cause of metastasis. Though KIBRA is one of the component of Hippo Pathway and is reported as tumor suppressor but this scaffolding protein has also been found to be an emerging and important player in the process of metastasis. It has been reported that KIBRA protein interacts with various proteins through its domain and leads cytoskeleton arrangement, cell polarity and migration. N terminal and C terminal of the protein contains the WW, Internal C2 & putative class III PDZ domain that interacts with DDR1, DLC1 & PKC? and helps the breast cancer cells to metastasize. To study whether KIBRA is involved in breast cancer metastasis, we checked its expression at both protein and mRNA level by Immunoblotting and Real Time PCR which showed increased KIBRA expression in ER positive cells. Further investigation to elucidate the role of KIBRA in ER positive cells, ER transfection and immunoblotting in triple negative breast cancer cell lines were performed, which indicated that ER leads to enhanced KIBRA expression in breast cancer cells.
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    Expression of CHAC1 in Breast Cancer Cell Lines
    (Central University of Punjab, 2018) Sharma, Ankita; Chander, Harish
    Breast cancer is the commonly diagnosed type of cancer in women and is a major cause of deaths in women. Unfolded Protein Response Pathway is a signaling pathway induced in endoplasmic reticulum as a stress response. This type of stress signaling has been seen to be activated in many tumors including breast cancer. CHAC1 (Glutathione specific gamma- glutamylcyclotransferas-1) is a member of UPR Pathway. It was first discovered as a component of the ATF4 arm of the UPR pathway in a co-regulated group of genes. CHAC1 expression is necessary and sufficient to induce well-characterized markers of apoptosis. CHAC1 is involved in the inhibition of TNFRS6B via ATF4-ATF3-CHOP signaling. This sensitizes cells to commit to apoptosis following induction of UPR pathway. Although CHAC1 is a pro-apoptotic component of the UPR pathway, its expression in breast cancers have been noted to be remarkably high. To study the role of CHAC1 in breast cancer, we analyzed the expression of CHAC1 at mRNA level by using Real-Time PCR and further checked its' protein expression by Western-blotting. Its expression was found to be higher in ER positive cells as compared to the ER negative cells. Further investigations were performed by transfecting MDA-MB-231 cells by ER-alpha, which confirmed that presence of ER-alpha leads to the higher expression cHAC1 in breast cancer cells.