Does loss of PRH alter the sensitivity of Dasatinib in breast tumour cells

[摘要] Breast cancer is the most common type of cancer to cause death in the UK (Cancer Research UK, 2014). Current therapeutic treatment has achieved significant success in reducing mortality rates but there are still a minority of patients for whom treatment is unsuccessful. A form of targeted therapy for breast cancer is the treatment with the Src/ABL inhibitor, Dasatinib. This project explores whether the transcription factor Proline Rich Homeodomain (PRH) mediates dasatinib sensitivity in breast tumour cells. Here we show that immortalised, non-tumour MCF-10A control cells are more sensitive to dasatinib than MCF-10A PRH knockdown cells Similarly, tumorigenic MCF-7 control cells are more sensitive to dasatinib treatment than MCF-7 PRH knockdown cells suggesting that in both of these cell types reduced viability following dasatinib treatment is mediated in part through PRH. In contrast, no significant difference in dasatinib sensitivity was found between the highly metastatic MDA-MB-231 control cells and MDA-MB-231 PRH knockdown cells. However, MDA-MB-231 control cells are more sensitive to dasatinib treatment than MCF-7 and MCF-10A control cells. We further investigated the molecular mechanism by which dasatinib sensitivity is mediated through PRH in the MCF-7 control and MCF-7 PRH knockdown cells. This thesis therefore demonstrates the potential role of PRH as a biomarker for dasatinib treatment of luminal breast cancer patients.

[发布机构] University:University of Birmingham;Department:School of Immunity and Infection

[关键词] R Medicine;RC Internal medicine;RC0254 Neoplasms. Tumors. Oncology (including Cancer)