Functional analysis of AP-2γ as an estrogen receptor α (ERα) cofactor in breast cancer.

• Main Author: Png, Jasmine Jie Min.
• Other Authors: Edwin Chong Wing Cheung
• Format: Final Year Project
• Language: English
• Published: 2011
• Subjects: DRNTU::Science::Biological sciences::Biochemistry
• Online Access: http://hdl.handle.net/10356/45111
• Institution: Nanyang Technological University

To functionally analyze the role of AP-2γ as an ERα cofactor in breast cancer, we focused on examining the phenotypic role of AP-2γ in breast cancer and question if AP-2γ is able to reprogram the transcriptional network of ERα. From our knockdown experiments in MCF-7, we had demonstrated that AP-2γ is not involved in cellular proliferation. Instead, it promotes breast cancer by mediating cell survival. Furthermore, we showed that AP-2γ silencing resulted in the down-regulation of ERα-upregulated genes, and this was verified by our over- expression experiments in U2OS Tet-on-ERα, a cell line that lacks AP-2γ expression. Hence, it can be ascertained that AP-2γ is required for the transcription of ERα-regulated genes. However, we observed a minimal effect on promoting cell survival after over-expression of AP-2γ in U2OS Tet-on-ERα. Such phenomenon could be explained by the requirement of other transcription factors that might cooperate with AP-2γ in the reprogramming machinery. Despite the partial reprogramming ability, we noticed a significant reduction in cell death in EtOH-treated U2OS Tet-on-ERα. Therefore, we can suggest that AP-2γ is able to reprogram the ERα transcription network to a certain extent.