ErbB2/Neu overexpression is observed in 20--30% of human mammary carcinomas and correlates with poor prognosis. We have demonstrated that four ErbB2/Neu tyrosine autophosphorylation sites (YB, YC, YD and YE) are sufficient to mediate transforming signals in vitro and bind distinct adapter proteins, suggesting that transformation functions through distinct pathways. To study the role of each individual tyrosine autophosphorylation site in mammary tumourigenesis, we derived transgenic mice expressing mutant ErbB2/Neu receptors in the mammary gland. Recently, we showed that YB and YD female transgenic mice developed mammary tumours with differences in tumour latency, morphology, and metastatic potential. To further understand the role of the autophosphorylation sites, I characterized the YC and YE transgenic mouse models and showed that although, they exhibit similar phenotypes, they also differ in their latency, morphology and metastatic rate compared to the YB and YD transgenic mouse models. This suggests that recruitment of specific adaptor proteins has distinct biological effects on ErbB2/Neu-mediated mammary tumourigenesis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.112529 |
| Date | January 2008 |
| Creators | Lam, Sonya Hoan Linh. |
| 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 Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002699542, proquestno: AAIMR51297, Theses scanned by UMI/ProQuest. |
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