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Role of the Nuclear Receptor PPAR款 in Clear Cell Renal and Bladder Urotheial Carcinoma
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Role of the Nuclear Receptor PPAR款 in Clear Cell Renal and Bladder Urotheial Carcinoma. |
| 개인저자 | Sanchez, Danielle J. |
| 단체저자명 | University of Pennsylvania. Cell and Molecular Biology. |
| 발행사항 | [S.l.]: University of Pennsylvania., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 117 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-03B. Dissertation Abstract International |
| ISBN | 9781085621922 |
| 학위논문주기 | Thesis (Ph.D.)--University of Pennsylvania, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: Simon, M Celeste. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR款) has a well-characterized role in the developmental process of adipogenesis and transcriptional regulation of lipid metabolism. However, its expression patterns and functions in various cancer subtypes are less understood. My studies investigate the role of PPAR款 in two distinct cancers of the urinary tract: clear cell renal cell carcinoma (ccRCC) and bladder urothelial carcinoma (UC). In ccRCC, I hypothesized that PPAR款 activity contributes to the aberrant lipid accumulation phenotype characteristic of this disease, thereby promoting tumor progression. Through ChIP-seq, I demonstrated that PPAR款 and its heterodimeric DNA binding partner retinoid X receptor (RXR) occupy both adipose-shared and ccRCC-specific sites throughout the genome. However, based on a number of in vitro and in vivo assays evaluating ccRCC viability, proliferation, migration, and effects on lipid metabolism, I concluded that PPAR款 was dispensable for these processes and ccRCC progression. I also studied the role of PPAR款 in UC, a cancer which displays copy number amplification and mRNA overexpression of PPARG or RXRA in ~30% oftumors. In contrast to the results obtained in ccRCC, I demonstrated that genetic and pharmacological inhibition of PPAR款 reduces tumor growth via cell cycle arrest. Furthermore, I identified a candidate list of PPAR款-regulated genes in UC based on ChIP- and RNA-seq analyses of cell culture models, as well as gene expression data from primary patient samples. Together, my studies illuminate the remarkable cell type-specific functions of PPAR款 in urinary tract cancers, and provide rationale for the pharmacological targeting of its transcriptional effectors in a subset of tumors. |
| 일반주제명 | Molecular biology. Cellular biology. Physiology. Epidemiology. Genetics. Public health. Oncology. Pathology. Health sciences. |
| 언어 | 영어 |
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