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Lucien McBeth_Thesis_6_22_16.pdf (3.23 MB)

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Glucocorticoid Receptor beta Increases the Migration of Human Urothelial Carcinoma Cells

McBeth, Lucien Reiter
http://orcid.org/0000-0002-7769-7876
http://rave.ohiolink.edu/etdc/view?acc_num=mco1467031531

Abstract Details

2016, Master of Science in Biomedical Sciences (MSBS), University of Toledo, Biomedical Sciences (Cardiovascular and Metabolic Diseases).
Urothelial carcinoma is one of the most prevalent cancers encountered in the country, and recent investigations demonstrate the important role of glucocorticoid signaling in the disease. We have shown that an alternate isoform of the glucocorticoid receptor (GR), GRß, causes migration of human urothelial carcinoma cells. We begin with a literature review of the role of GRß and another nuclear receptor, the androgen receptor, in urothelial carcinoma. Next, we investigate the role of GRß in the migration of human urothelial carcinoma cells in two transitional human uroepithelial carcinoma cells, UMUC-3 and T24. We found that the T24 cells have higher GRß expression compared to the UMUC-3, and that both cell lines had a similar GRa level. Interestingly, the higher GRß expression was correlated with enhanced migration rates, which was reduced with GRß inhibition. In-silco analysis of the 3’ untranslated region (3’UTR) of human GRß revealed a potential micro-RNA (miRNA) binding site for miR33a, miR144, and miR181. Therefore, we cloned the 3’UTR of human GRß and mutated the miRNA binding sites, which showed that miR144 positively regulates GRß expression. In addition, miR144 and GRß expression were increased during migration of uroepithelial carcinoma cells. Therefore, we constructed a peptide nucleic acid (PNA) conjugated to a cell penetrating-peptide (CPP) that we termed Sweet-P to inhibit the miR144 binding site in the 3’UTR of human GRß. Furthermore, Sweet-P decreased GRß expression and, as a result, inhibited migration of uroepithelial carcinoma cells, demonstrating its potential as a therapeutic. We then complete the thesis with a discussion of the potential for Sweet-P in cancer therapy and other GRß-related diseases, which may serve as the first anti-GRß drug.
Terry Hinds, Jr (Committee Chair)
Edwin Sanchez (Committee Member)
Beata Lecka-Czernik (Committee Member)
Nitin Puri (Committee Member)
120 p.
Biomedical Research
Glucocorticoid receptor; GR; GR alpha; GR beta; glucocorticoids; androgens; androgen receptor; AR; cancer; bladder cancer; males; growth; inflammation; microRNA; miRNA; migration; asthma; Sweet-P

Recommended Citations

Citations

  • McBeth, L. R. (2016). Glucocorticoid Receptor beta Increases the Migration of Human Urothelial Carcinoma Cells [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1467031531

    APA Style (7th edition)

  • McBeth, Lucien. Glucocorticoid Receptor beta Increases the Migration of Human Urothelial Carcinoma Cells. 2016. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1467031531.

    MLA Style (8th edition)

  • McBeth, Lucien. "Glucocorticoid Receptor beta Increases the Migration of Human Urothelial Carcinoma Cells." Master's thesis, University of Toledo, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=mco1467031531

    Chicago Manual of Style (17th edition)

mco1467031531
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This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.