Abstract
Nearly 40,000 women die annually from breast cancer in the US. Clinically available targeted breast cancer therapy is ineffective in triple negative breast cancer (TNBC) subtypes, which lack expression of the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. TNBC carries a poor prognosis. Previous reports show that aryl hydrocarbon receptor (AhR) agonist 2-(4-amino-3-methylphenyl)- 5-fluorobenzothiazole (5F 203) selectively inhibits the growth of breast cancer cells including those of the TNBC subtype. In the current study, we determined that 5F 203 induces the expression of epigenetically silenced putative tumor suppressor gene cytoglobin (CYGB) and suppresses TNBC cell growth in vitro and in vivo. Additionally, 5F 203 induces the expression of pro-apoptotic genes and promotes TNBC cell death, in part, via CYGB upregulation. These data provide a basis for the development of AhR agonists with potential to restore CYGB expression as a strategy to treat TNBC.
LLU Discipline
Biochemistry
Department
Biochemistry
School
School of Medicine
First Advisor
Eileen J. Brantley
Second Advisor
Carlos A. Casiano
Third Advisor
Daisy D. De León
Fourth Advisor
Christopher Perry
Fifth Advisor
Juli Unternaehrer
Sixth Advisor
Charles Wang
Degree Name
Doctor of Philosophy (Medical Science)
Degree Level
Ph.D.
Year Degree Awarded
2019
Date (Title Page)
8-2018
Language
English
Library of Congress/MESH Subject Headings
Triple Negative Breast Neoplasms; Receptors, Aryl Hydrocarbon; Cytoglobin
Type
Dissertation
Page Count
xvii, 138 p.
Digital Format
Digital Publisher
Loma Linda University Libraries
Copyright
Author
Usage Rights
This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.
Recommended Citation
Rowland, Leah Kathleen, "Aryl Hydrocarbon Receptor Mediated Restoration of Cytoglobin as a Treatment for Breast Cancer" (2018). Loma Linda University Electronic Theses, Dissertations & Projects. 1788.
https://scholarsrepository.llu.edu/etd/1788
Collection
Loma Linda University Electronic Theses and Dissertations
Collection Website
http://scholarsrepository.llu.edu/etd/
Repository
Loma Linda University. Del E. Webb Memorial Library. University Archives