Contribution of different estrogen receptor alpha (ER) domains in ER-driven transcriptomic profile of mammary epithelial cells and characterization of the ER-PR proximity in ER+ breast cancer

Šantek, Iva

Embargo period 2030-01-01

master's thesis

Contribution of different estrogen receptor alpha (ER) domains in ER-driven transcriptomic profile of mammary epithelial cells and characterization of the ER-PR proximity in ER+ breast cancer

2020. urn:nbn:hr:193:356171

Šantek, Iva

University of Rijeka
Faculty of Biotechnology and Drug Development

Cite this document

APA 6th Edition

Šantek, I. (2020). Contribution of different estrogen receptor alpha (ER) domains in ER-driven transcriptomic profile of mammary epithelial cells and characterization of the ER-PR proximity in ER+ breast cancer (Master's thesis). Rijeka: University of Rijeka. Retrieved from https://urn.nsk.hr/urn:nbn:hr:193:356171

MLA 8th Edition

Šantek, Iva. "Contribution of different estrogen receptor alpha (ER) domains in ER-driven transcriptomic profile of mammary epithelial cells and characterization of the ER-PR proximity in ER+ breast cancer." Master's thesis, University of Rijeka, 2020. https://urn.nsk.hr/urn:nbn:hr:193:356171

Chicago 17th Edition

Harvard

Šantek, I. (2020). 'Contribution of different estrogen receptor alpha (ER) domains in ER-driven transcriptomic profile of mammary epithelial cells and characterization of the ER-PR proximity in ER+ breast cancer', Master's thesis, University of Rijeka, accessed 08 May 2024, https://urn.nsk.hr/urn:nbn:hr:193:356171

Vancouver

Šantek I. Contribution of different estrogen receptor alpha (ER) domains in ER-driven transcriptomic profile of mammary epithelial cells and characterization of the ER-PR proximity in ER+ breast cancer [Master's thesis]. Rijeka: University of Rijeka; 2020 [cited 2024 May 08] Available at: https://urn.nsk.hr/urn:nbn:hr:193:356171

IEEE

I. Šantek, "Contribution of different estrogen receptor alpha (ER) domains in ER-driven transcriptomic profile of mammary epithelial cells and characterization of the ER-PR proximity in ER+ breast cancer", Master's thesis, University of Rijeka, Rijeka, 2020. Available at: https://urn.nsk.hr/urn:nbn:hr:193:356171

Cite this item: https://urn.nsk.hr/urn:nbn:hr:193:356171

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Metadata

Title	Contribution of different estrogen receptor alpha (ER) domains in ER-driven transcriptomic profile of mammary epithelial cells and characterization of the ER-PR proximity in ER+ breast cancer
Author	Iva Šantek
Mentor	prof. dr. sc. Cathrin Brisken (mentor)
Granter	University of Rijeka (Faculty of Biotechnology and Drug Development) Rijeka
Defense date and country	2020-12-18, Croatia
Scientific / art field, discipline and subdiscipline	BIOTECHNICAL SCIENCES Biotechnology
Abstract	Aim of the study: 70% of breast cancers (BC) are estrogen receptor alphapositive (ER+), and typically treated by targeting ER signaling. Previous research showed that membrane ER, as well as activation function 1 (AF-1) and activation function 2 (AF-2) domains are involved in the mammary gland and BC development. We aimed to characterize the contribution of each ER domain in ER regulated transcriptional profile in mammary epithelial cells (MEC). First, we researched whether ER-dependent gene expression is domain-specific. We tested the hypothesis that pathways relevant for BC are ER domain-dependent, and aimed to characterize whether those pathways are regulated by the cooperation of all domains or by an individual domain. We focused on the dependences of the expression of ER target genes, such as Areg, Greb1, and Pgr on different ER domains. Finally, we aimed to characterize the levels of interactions between PR and ER in cancer cell lines MCF7 and T47D. Material and methods: In this thesis, RNAseq data of GFP+ MECs from C57Bl6 mice lacking complete ER, membrane ER, AF-1 or AF-2 ER domains were analyzed in R software. MCF7 and T47D cell lines were treated with 100 nM progesterone (P4) to establish the conditions suitable for ER-PR interactions. The expression of Pgr was measured by qPCR and ER-PR interactions were analyzed by proximity ligation assay. Results and conclusions: Each ER domain strongly contributes to ER-regulated gene expression in MECs. To regulate pathways involved in carcinogenesis, cell proliferation, and immune response, ER domains act synergically, but also, in some pathways, an individual domain plays a regulatory role of the whole receptor. ER-PR direct interactions occur in nuclei, but also in non-nuclear compartments in MCF7 and T47D cells with an increased number of interactions upon P4 treatment.
Keywords
Language	english
URN:NBN	urn:nbn:hr:193:356171
Study programme	Title: Drug research and development Study programme type: university Study level: graduate Academic / professional title: magistar/magistra istraživanja i razvoja lijekova (magistar/magistra istraživanja i razvoja lijekova)
Type of resource	Text
File origin	Born digital
Access conditions	Embargoed access Embargo expiration date: 2030-01-01
Terms of use
Created on	2021-01-11 13:30:25