Regulation of estrogen receptor alpha by promoter methylation, alternative splicing and microRNA
Albrecht, Juliane LU
(2024)
In Lund University, Faculty of Medicine Doctoral Dissertation Series
- Abstract
- Breast cancer, a common and often aggressive malignancy, presents significant challenges due to its ability to develop resistance to therapies. This resistance is intricately linked to the function and regulation of the estrogen receptor, a key driver of breast cancer cell proliferation. Our research focuses on unraveling the complex mechanisms underlying this resistance by investigating the roles
of estrogen receptor isoforms, epigenetic modifications, and microRNAs (miRNAs). Through comprehensive analyses, we demonstrate that the estrogen receptor undergoes alternative splicing, producing multiple isoforms with distinct functional properties. These isoforms vary in their sensitivity to breast cancer therapies, potentially leading to... (More) - Breast cancer, a common and often aggressive malignancy, presents significant challenges due to its ability to develop resistance to therapies. This resistance is intricately linked to the function and regulation of the estrogen receptor, a key driver of breast cancer cell proliferation. Our research focuses on unraveling the complex mechanisms underlying this resistance by investigating the roles
of estrogen receptor isoforms, epigenetic modifications, and microRNAs (miRNAs). Through comprehensive analyses, we demonstrate that the estrogen receptor undergoes alternative splicing, producing multiple isoforms with distinct functional properties. These isoforms vary in their sensitivity to breast cancer therapies, potentially leading to differential treatment outcomes.
Additionally, we explored how DNA methylation in regulatory regions of the estrogen receptor gene influences the expression and function of these isoforms, revealing a crucial layer of epigenetic control that could contribute to therapy resistance. Furthermore, our study identifies the miRNA miR-4728-3p, encoded by the ERBB2 oncogene, as a significant regulator of estrogen synthesis in breast cancer cells. By modulating the levels of aromatase and other estrogen-related enzymes, miR-4728-3p plays a pivotal role in the intricate network of factors driving breast cancer progression and resistance to treatment. These findings enhance our understanding of the multifaceted mechanisms of breast cancer resistance, providing valuable insights that could inform the development of more effective therapeutic strategies. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/79a3754f-86c0-4304-b3e1-8d2ab7b78b25
- author
- Albrecht, Juliane
LU
- supervisor
- opponent
-
- PhD Kutter, Claudia, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
- organization
- publishing date
- 2024
- type
- Thesis
- publication status
- published
- subject
- keywords
- Estrogen Receptor alpha, breast cancer, Methylation, microRNA, Alternative Splicing
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2024:123
- pages
- 134 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Belfragesalen, BMC D15, Klinikgatan 32 i Lund. Join by Zoom: https://lu-se.zoom.us/j/69146273109?pwd=dW4qKH1RXSzP55eM46wmUjS2Pyv6bz.1
- defense date
- 2024-10-23 09:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-620-3
- language
- English
- LU publication?
- yes
- id
- 79a3754f-86c0-4304-b3e1-8d2ab7b78b25
- date added to LUP
- 2024-09-26 17:14:38
- date last changed
- 2025-04-04 14:03:06
@phdthesis{79a3754f-86c0-4304-b3e1-8d2ab7b78b25,
abstract = {{Breast cancer, a common and often aggressive malignancy, presents significant challenges due to its ability to develop resistance to therapies. This resistance is intricately linked to the function and regulation of the estrogen receptor, a key driver of breast cancer cell proliferation. Our research focuses on unraveling the complex mechanisms underlying this resistance by investigating the roles<br/>of estrogen receptor isoforms, epigenetic modifications, and microRNAs (miRNAs). Through comprehensive analyses, we demonstrate that the estrogen receptor undergoes alternative splicing, producing multiple isoforms with distinct functional properties. These isoforms vary in their sensitivity to breast cancer therapies, potentially leading to differential treatment outcomes.<br/>Additionally, we explored how DNA methylation in regulatory regions of the estrogen receptor gene influences the expression and function of these isoforms, revealing a crucial layer of epigenetic control that could contribute to therapy resistance. Furthermore, our study identifies the miRNA miR-4728-3p, encoded by the ERBB2 oncogene, as a significant regulator of estrogen synthesis in breast cancer cells. By modulating the levels of aromatase and other estrogen-related enzymes, miR-4728-3p plays a pivotal role in the intricate network of factors driving breast cancer progression and resistance to treatment. These findings enhance our understanding of the multifaceted mechanisms of breast cancer resistance, providing valuable insights that could inform the development of more effective therapeutic strategies.}},
author = {{Albrecht, Juliane}},
isbn = {{978-91-8021-620-3}},
issn = {{1652-8220}},
keywords = {{Estrogen Receptor alpha; breast cancer; Methylation; microRNA; Alternative Splicing}},
language = {{eng}},
number = {{2024:123}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Regulation of estrogen receptor alpha by promoter methylation, alternative splicing and microRNA}},
url = {{https://lup.lub.lu.se/search/files/195911367/Thesis_Juliane_Albrecht_LUCRIS.pdf}},
year = {{2024}},
}