Obesity is an adverse factor in the development and severity of breast cancer. Obesity is
often accompanied by an increase in circulating insulin, which is also associated with
poor BC prognosis. Although not expressed in normal breast tissue, the insulin receptor
(IR) is highly expressed in BC, therefore insulin signaling in BC cells may be responsible
for the negative prognostic effects associated with hyperinsulinemia.
This thesis describes the development of a cell-based system to study how insulin affects
BC. My work shows that MCF10A, untransformed human breast epithelial cells that
express the IR, require insulin for normal proliferation and morphology. Interestingly, I
discovered hyperactivation of ERK1/2 in MCF10A cells in response to insulin
withdrawal, resulting in a loss of epithelial phenotype. Unexpectedly, while losing
epithelial phenotype, MCF10A cells depleted of insulin failed to migrate. In conclusion,
breast cells that express IR require insulin for migration and maintenance of epithelial
characteristics.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/35599 |
| Date | 11 July 2013 |
| Creators | Di Palma, Vanessa C. |
| Contributors | Stambolic, Vuk |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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