| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000432874 |
| 005 | | 20200225103302 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781085621922 |
| 035 | |
▼a (MiAaPQ)AAI13865100 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 614 |
| 100 | 1 |
▼a Sanchez, Danielle J. |
| 245 | 10 |
▼a Role of the Nuclear Receptor PPAR款 in Clear Cell Renal and Bladder Urotheial Carcinoma. |
| 260 | |
▼a [S.l.]:
▼b University of Pennsylvania.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 117 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-03, Section: B. |
| 500 | |
▼a Advisor: Simon, M Celeste. |
| 502 | 1 |
▼a Thesis (Ph.D.)--University of Pennsylvania, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 520 | |
▼a 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. |
| 590 | |
▼a School code: 0175. |
| 650 | 4 |
▼a Molecular biology. |
| 650 | 4 |
▼a Cellular biology. |
| 650 | 4 |
▼a Physiology. |
| 650 | 4 |
▼a Epidemiology. |
| 650 | 4 |
▼a Genetics. |
| 650 | 4 |
▼a Public health. |
| 650 | 4 |
▼a Oncology. |
| 650 | 4 |
▼a Pathology. |
| 650 | 4 |
▼a Health sciences. |
| 690 | |
▼a 0307 |
| 690 | |
▼a 0379 |
| 690 | |
▼a 0573 |
| 690 | |
▼a 0571 |
| 690 | |
▼a 0566 |
| 690 | |
▼a 0992 |
| 690 | |
▼a 0369 |
| 690 | |
▼a 0766 |
| 690 | |
▼a 0719 |
| 710 | 20 |
▼a University of Pennsylvania.
▼b Cell and Molecular Biology. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-03B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0175 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15491042
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1816162 |
| 991 | |
▼a E-BOOK |