Thesis
Prednisone-induced resistance in canine multicentric lymphoma: A clinical and molecular approach to understanding the role of NR3C1, ABCB1 (MDR1), 11B-HSD1, and 11B-HSD2
Washington State University
Master of Science (MS), Washington State University
07/2018
DOI:
https://doi.org/10.7273/000004133
Handle:
https://hdl.handle.net/2376/125178
Abstract
Resistance to prednisone develops rapidly and essentially universally when dogs with lymphoma are treated with corticosteroids such as prednisone. We studied naturally occurring mechanisms of prednisone resistance by assessing the level of expression of the following genes in dogs with clinical evidence of prednisone resistance: the glucocorticoid receptor NR3C1, ABCB1 (formerly MDR1), 11B-HSD1, and 11B-HSD2. We hypothesized that, when compared to pre-treatment samples, prednisone-resistant lymphoma samples, would have (1) decreased NR3C1 and 11B-HSD1 expression; (2) increased 11B-HSD2 expression and (3) unchanged ABCB1 expression. To test this hypothesis, seven dogs with naïve multicentric lymphoma were enrolled prospectively and treated with daily oral prednisone. Gene expression of NR3C1, ABCB1, 11B-HSD1, and 11B-HSD2 in lymph nodes was evaluated by real time RT-PCR. Expression levels at diagnosis and at time of clinical resistance to prednisone were compared longitudinally using a Wilcoxon signed-rank test. Dogs were treated with prednisone for a median of 68 days (range, 7 to 201 days). Relative to pretreatment samples, prednisone treatment was associated with decreased expression of the NR3C1 gene in lymph node biopsies of all dogs with high-grade lymphoma when clinical resistance to prednisone was observed (6 dogs, p=0.031). Interestingly, one dog with indolent T-zone lymphoma had increased expression of NR3C1. Resistance could not be consistently attributed to variations in ABCB1, 11B-HSD1 or 11B-HSD2 expression. Marked increase of the expression of 11B-HSD1 or 11B-HSD2 was exhibited in 2 dogs. In conclusion, decreased expression of the glucocorticoid receptor (NR3C1 gene) may play a role in conferring resistance to prednisone in dogs with lymphoma. Results do not indicate a broad role for ABCB1, 11B-HSD1 and 11B-HSD2 in the emergence of prednisone resistance in dogs with lymphoma.
Metrics
Details
- Title
- Prednisone-induced resistance in canine multicentric lymphoma
- Creators
- Camille Clemence Hanot
- Contributors
- Rance Sellon (Advisor) - Washington State University, Veterinary Clinical Sciences, Department of
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Identifiers
- 99900890781501842
- Language
- English
- Resource Type
- Thesis