Electronic Thesis and Dissertation Repository


Master of Science




Dr. Christopher J. Howlett

2nd Supervisor

Dr. Douglas Quan

Joint Supervisor


Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare type of malignant epithelial cancer arising from the diffuse neuroendocrine system. In this study, we have performed gene expression profiling along with immunohistochemistry (IHC) to highlight key molecular pathways underlying the pathogenesis of GEP-NETs. We used formalin-fixed paraffin-embedded archived tissue samples of NETs arising from small intestine (SI-NETs), pancreas (P-NETs), and distal colon/rectal region (R-NETs) to extract RNA for real-time PCR-based gene profiling, and to construct tissue microarrays (TMAs) for high-throughput immunohistochemistry. Our results show evidence of epithelial to mesenchymal transition (EMT) at the mRNA and protein levels. From the genes highlighted by our gene expression studies, TGF-β/BMP signaling could be a key mediator towards this EMT event. Therefore, we investigated whether TGF-β signaling is active in GEP-NETs and determined whether its activation is linked to an EMT phenotype.

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