The role of the proline rich homeodomain in the regulation of proliferation, survival and migration of breast cells

[摘要] This thesis demonstrates that the Proline Rich Homeodomain transcription factor (PRH/HHEX) plays an important role in regulating the proliferation and migratory behaviour of breast cells. In tumourigenic MCF-7 breast cells, shRNA knockdown of PRH results in a pro-invasive and pro-proliferative phenotype. Key genes regulated by PRH in MCF-7 cells include TP53, endoglin (ENG) and e-cadherin (CDH1), which regulate migration/invasion in breast cells. Significantly, exogenous PRH functions as an inhibitor of cell proliferation/survival and migration/invasion in all breast cell types examined. Furthermore, the effects of exogenous PRH on cell proliferation/survival are dependent on the DNA binding activity of PRH. This work provides an explanation for the finding that PRH expression is associated with increased overall survival in breast cancer patients. In contrast with this work, MCF-7 xenograft experiments reveal that expression of exogenous PRH in MCF-7 cells is oncogenic. Furthermore, shRNA knockdown experiments in MDA-MB-231 cells show that endogenous PRH increases proliferation of these cells. This thesis therefore demonstrates that the role of PRH can differ dramatically between breast cell types and between ex vivo and in vivo conditions.

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

[关键词] R Medicine;R Medicine (General)