ROLE OF EPIDERMAL GROWTH FACTOR RECEPTOR ON CARDIAC FUNCTION
Public DepositedAdd to collection
You do not have access to any existing collections. You may create a new collection.
Downloadable Content
Download PDFCitation
MLA
Xie, Yuying. Role Of Epidermal Growth Factor Receptor On Cardiac Function. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School, 2015. https://doi.org/10.17615/mm5j-e427APA
Xie, Y. (2015). ROLE OF EPIDERMAL GROWTH FACTOR RECEPTOR ON CARDIAC FUNCTION. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School. https://doi.org/10.17615/mm5j-e427Chicago
Xie, Yuying. 2015. Role Of Epidermal Growth Factor Receptor On Cardiac Function. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School. https://doi.org/10.17615/mm5j-e427- Last Modified
- March 19, 2019
- Creator
-
Xie, Yuying
- Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
- Abstract
- The epidermal growth factor receptor (EGFR/ERBB1) was the first discovered member of the ERBB family of tyrosine kinas receptors that includes ERBB2, ERBB3 and ERBB4. After binding by EGF-related ligands, EGFR is activated to induce homodimerization or heterodimerization with other ERBB receptors, resulting in tyrosine kinase activity. Subsequently, autophosphorylation or transphosphorylation of tyrosine residues in the C-terminal tail of the receptor allows the binding of adaptor proteins to trigger intracellular signaling cascades that can lead to proliferation, survival, and anti-apoptosis. As EGFR is expressed in the majority of developing and adult tissues including heart, dysfunction of EGFR activity can cause severe damage in different tissues and even initiate cancers. Several anti-EGFR drugs are already available in the clinic for late stage cancer patients with activated EGFR activity. However, in cancer therapy using anti-ERBB2 drugs, severe cardiotoxicity among patients has been reported, emphasizing the importance of ERBB signaling in cardiac homeostasis. Also with the increases in life expectancy of patients, some types of cancers tend to be treated as a chronic disease. Therefore it is importance to understanding possible cardiac toxicity under chronic suppression of EGFR pathway. We propose the use of conditional knockout mice lacking EGFR activity in cardiomyocytes to understand the role of EGFR signaling in normal cardiac function. We demonstrated that chronic repression of EGFR pathway would cause severe cardiac dysfunction with chamber dilations, left ventricular wall thinning and depressed cardiac function. Left ventricular hypertrophy (LVH) is associated with many cardiovascular diseases and is a risk factor for cardiac related morbidity and mortality. Mice homozygous with EGFR hypomorphic mutation display various background dependent phenotypes including left ventricle hypertrophy. Using two different strains, we mapped a quantitative trait locus (QTL) associated with cardiac hypertrophy. These studies should be useful in understanding the development of LVH and in predicting patients susceptible to cardiatoxicity induced by chronic use of anti-EGFR drugs.
- Date of publication
- May 2015
- Keyword
- Subject
- DOI
- Identifier
- Resource type
- Rights statement
- In Copyright
- Advisor
- Manuel Pardo-Pardo-Manuel de Villena, Fernando
- Sun, Wei
- Threadgill, David W.
- Wang, Wei
- Wiltshire, Timothy
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2015
- Language
- Publisher
- Place of publication
- Chapel Hill, NC
- Access right
- There are no restrictions to this item.
- Date uploaded
- June 23, 2015
Relations
- Parents:
This work has no parents.
Items
Thumbnail | Title | Date Uploaded | Visibility | Actions |
---|---|---|---|---|
Xie_unc_0153D_15129.pdf | 2019-04-11 | Public | Download |