Master of Science in Molecular Pathology and Immunology
Graduate School of Biomedical Sciences
School of Osteopathic Medicine
Genesis Biotechnology Group
Rachael Siegel, PhD
Committee Member 1
Ilana Stroke, PhD
Committee Member 2
Jim Beasley, PhD
Cadherins; Zinc Finger E-box-Binding Homeobox 1; Endometrial Neoplasms; Histone Deacetylase Inhibitors
Cancer Biology | Cell Biology | Female Urogenital Diseases and Pregnancy Complications | Laboratory and Basic Science Research | Medicine and Health Sciences | Molecular Biology | Molecular Genetics | Neoplasms
Epithelial to mesenchymal transition (EMT) is the process in which cells lose their epithelial structure during gastrulation. This process also affects the migration and movement of tumor cells and promotes invasion and metastases of endometrial carcinomas. Down-regulation of E-cadherin (CDH1) by transcription factors is the key target of EMT modulators and is achieved mainly by ZEB1 (zinc finger E-box binding homeobox 1). Current research looking at restoration of E-cadherin expression in vitro involves the use of small molecules such as histone deacetylase (HDAC) inhibitors and DNA methyltransferase inhibitors. Trichostatin A (TSA) and small interfering ribonucleic acid (siRNA) are tools that can be used to induce CDH1 activity.
To identify a cell line that is suitable for testing novel compounds and capable of increasing E-cadherin expression via ZEB1 inhibition, two uterine adenocarcinoma cell lines (AN3CA and SK-UT-1B), stably transfected with an E-cadherin promoter reporter gene, were characterized using various assays. Novel, small molecule compounds were tested on a colon cancer cell line (SW620/CDH1-NLuc) and showed enhancement of CDH1 reporter activity. In this thesis research several assays were performed to test our hypothesis that modulating ZEB1 using small molecules may lead to an increase in the expression of E-cadherin in endometrial cancers and CDH1 responsiveness to the small molecules in endometrial cancer cell lines will be observed.
Chukwu, Chidozie Paul, "Characterization of E-Cadherin Regulation in Response to ZEB1 Inhibition in Endometrial Cancer Cell Lines" (2017). Graduate School of Biomedical Sciences Theses and Dissertations. 47.
Cancer Biology Commons, Cell Biology Commons, Female Urogenital Diseases and Pregnancy Complications Commons, Laboratory and Basic Science Research Commons, Molecular Biology Commons, Molecular Genetics Commons, Neoplasms Commons