The role of iron and haem in breast cancer

Roe, Thomas (2015). The role of iron and haem in breast cancer. University of Birmingham. M.D.

[img]
Preview
Roe15MD.pdf
PDF - Accepted Version

Download (7MB)

Abstract

Iron is ubiquitous in the human body, fulfilling many crucial roles. However, accumulating evidence implicates excess iron as a carcinogen. This study aimed to further investigate the role of iron and haem in breast carcinogenesis and the potential utility of chelators in therapy.

We demonstrate that the transport machinery for iron and haem is dysregulated in breast cancer, with import being promoted and export down-regulated to allow the accumulation of intra-cellular iron. In vitro studies demonstrate that, in contrast to benign cells, malignant cells are capable of importing haem as well as ionic iron. Both iron and haem stimulate aggressive behaviour in malignant cells, up-regulating viability, proliferation, adhesion, migration and invasion. These changes are abrogated by iron chelation. In addition, the expression profile of iron and haem transporters is shown to favour intra-cellular accumulation even when iron is plentiful and import would be expected to be down-graded.

Overall this study suggests that breast cancer may be due to an inappropriate expression profile of iron and haem transporters, leading to excess intra-cellular iron which drives a malignant cell phenotype. In addition the action of chelators to downgrade malignant behaviour implies a potential therapeutic role.

Type of Work: Thesis (Higher Doctorates > M.D.)
Award Type: Higher Doctorates > M.D.
Supervisor(s):
Supervisor(s)EmailORCID
Tselepis, ChrisUNSPECIFIEDUNSPECIFIED
Hoar, FionaUNSPECIFIEDUNSPECIFIED
Licence:
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Cancer Studies
Funders: Other
Other Funders: Birmingham City Hospital
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
URI: http://etheses.bham.ac.uk/id/eprint/6233

Actions

Request a Correction Request a Correction
View Item View Item

Downloads

Downloads per month over past year