Date of Award

Summer 2018

Document type

Thesis

Degree Name

PhD (Doctor of Philosophy)

First Supervisor

Professor Leonie Young

Second Supervisor

Professor Arnold Hill

Funder/Sponsor

Irish Cancer Society (Breast Predict)

Keywords

Breast Cancer, Metastases, Endocrine Resistance

Abstract

Approximately 70 % of breast cancer patients are classified as oestrogen receptor positive. While initial prognosis is favourable, the risk of recurrence remains long after diagnosis. Furthermore, the ability to treat recurrent tumours becomes harder over time as resistance to endocrine therapy develops. This resistant phenotype is caused in part by overexpression of the nuclear receptor co-activator SRC-1. Moreover, SRC-1 has been shown to promote metastatic development in several breast cancer models.

Previously, our lab identified the neuronal protein ADAM22 as an SRC-1 target gene involved in endocrine resistant breast cancer metastases. Here, this metastatic role was further characterised through knockdown, knockout and overexpression studies along with a high throughput proteomic study. This study demonstrates the potential of ADAM22 as a biomarker for predicting metastatic development in endocrine resistant patients. Finally, an ADAM22 targeting peptide mimetic was shown here to reverse ADAM22 mediated metastatic characteristics both in vitro and in vivo.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

File Size

4.38 MB

Comments

A thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2018.

Share

COinS