Date of Award
2010
Degree Type
Thesis
Degree Name
Master of Science
Program
Anatomy and Cell Biology
Supervisor
Dr. Lynne-Marie Postovit
Abstract
Recently, the stem cell factor Nodal has been correlated with metastatic competence in breast cancer. We investigated hypoxia as a regulator of Nodal as it is an important feature of stem and cancer cell microenvironments. We hypothesized that hypoxia up-regulates Nodal in poorly metastatic T47D breast cancer cells through the Hypoxia-Inducible Factor-1 (HIF-1) and Notch signalling pathways. We exposed cells to decreasing concentrations of O2 for varying amounts of time. 0.5% O2 for 48 h experienced a maximal induction of Nodal mRNA expression and protein levels, which persisted for up to 72 h with reoxygenation. HIF-lα over-expression and knock down experiments implicate a role for HIF-lα transcriptional regulation of Nodal. Dual luciferase assays, which investigated the Notch-responsive enhancer region (NDE) upstream of Nodal, showed activation in hypoxia. Mutations in the NDE abrogated this activity. This work reveals how a normally stem cell-associated factor can be up- regulated by hypoxia in cancer cells.
Recommended Citation
Taylor, Meghan J., "THE ROLE OF OXYGEN AS A REGULATOR OF NODAL EXPRESSION IN POORLY METASTATIC BREAST CANCER CELLS" (2010). Digitized Theses. 4542.
https://ir.lib.uwo.ca/digitizedtheses/4542