Protection from Endoplasmic Reticulum Stress and Apoptosis via PPARδ and Bcl-2 in Breast Cancer
Year: 2019
Type: dissertation
Abstract: Estrogen receptor positive breast cancer accounts for the majority of breast cancer cases. Anti-estrogens, such as tamoxifen, are used to prevent the growth and survival of these cancer cells. However, patients often develop resistance to this drug due to dysregulated apoptosis. The overexpression of either Bcl-2, an anti-apoptotic protein, or PPARδ, a nuclear receptor protein, allows cancer cells to evade endoplasmic reticulum stress and survive. MCF-7 cells were used to investigate how dysregulated apoptosis contributes to tamoxifen resistance. Synergistic protection was observed in cells that overexpressed both PPARδ and Bcl-2, suggesting that the proteins work through different pathways. This implies that patients would require different treatments depending on the expression levels of Bcl-2 and or PPARδ in their tumours. In addition, the Bcl-2 inhibitor, ABT-199, was unable to sensitize cells that overexpressed Bcl-2 to drug treatments that elicit endoplasmic reticulum stress, revealing a novel BH3-independent mechanism of resistance through Bcl-2.
Source: TSpace (University of Toronto)
Author: Hilary Wong
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2990293276