University of Texas Health Science Center at Houston
Understanding The Pathogenesis of Renal Medullary Carcinoma
Abstract
dc:description.abstract<p>Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the context of hypoxia. Overall, we proposed that the link between SCT and SMARCB1 deficiency observed in RMC is due to renal hypoxia, which promotes the loss of SMARCB1 due to its survival advantage in hypoxia.</p>
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy (PhD)
- Level thesis:degree_level
- Dissertation (PhD)
- Year dc:date.available
- 2021
Author and committee
dc:creator, dc:contributor.*- Authors dc:creator
-
- Soeung, Melinda
- <p>https://orcid.org/0000-0002-6902-898X</p>
- Contributors dc:contributor
-
- Giulio Draetta, MD, PhD
- Giannicola Genovese, MD, PhD
- Michelle Barton, PhD
Subjects
dc:subject × 14Identifiers
dc:identifier.*- Repository record dc:identifier
- https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1123
- OAI identifier oai:identifier
- oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2181