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

PDF

Digital Publisher

Loma Linda University Libraries

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.

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

Included in

Biochemistry Commons

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