The androgen receptor plays a critical role in both normal and neoplastic prostate growth. The first exon of the androgen receptor contains a polymorphic CAG repeat region that has been implicated in the development of prostate cancer. Epidemiologic studies suggest that shorter CAG repeats are associated with an increased risk of prostate cancer. Interestingly, the length of the CAG repeat region in the androgen receptor is inversely correlated with the transactivational competence of the receptor. This provides a biologically plausible mechanism by which the more active androgen receptors with shorter CAG repeats can contribute to prostate cancer. However, the effect of variation in CAG repeat length is unknown in the late-stages of the disease. / The primary goal of the work presented in this thesis was to determine the effects of different AR CAG repeat lengths in a late-stage prostate cancer environment where androgen receptor mutations are more common and may override the functional attributes of short CAG repeats. To that end, we have assessed the effects of CAG repeat lengths in a common prostate cancer mutant androgen receptor Thr877Ala. Our results suggest that the Thr877Ala mutant exhibits different transactivation trends than the wild-type receptor with respect to CAG repeat length. These data may indicate that, although CAG length may have a significant effect in wild-type receptors and in early disease, the activity of mutant receptors found in later stages of prostate cancer may limit the CAG effect.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.111933 |
| Date | January 2006 |
| Creators | Southwell, Jason M. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Human Genetics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002541491, proquestno: AAIMR28531, Theses scanned by UMI/ProQuest. |
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