Given the recent discovery of RUNX1 somatic mutations in biopsies of breast cancer patients, the overall purpose of the present thesis consists of using different in vivo and ex vivo experimental systems in the attempt to answer two main questions: firstly, if the Runx1 gene plays any causative role in the context of breast cancer; and secondly, if its putative function is symptomatic of a tumour suppressor gene and/or of a pro-oncogene. By characterizing the effects of Runx1 deletion in two different breast cancer mouse models (i.e. the MMTV-PyMT and the Wnt/β-catenin-driven models of mammary tumourigenesis), this thesis provides the first in vivo evidence of a dualistic role played by the gene in the context of breast cancer. Runx1 would in fact appear to act as a tumour suppressor at early stages of the disease, whilst as a pro-oncogene at later stages of mammary tumourigenesis. To fully comprehend the significance of these major findings, the introduction will first provide a brief description on the RUNX family of genes, as well as on the state-of-the-art knowledge of RUNX1’s role in both mammary gland and breast cancer biology. As such, particular attention will then be given not only to the ontogeny, endocrine regulation and composition of the murine mammary gland, yet also to the high degree of heterogeneity, the putative “cell-of-origin(s)” and the different experimental models commonly used to study breast cancer. Through the aforementioned rationale, it is hoped that the introduction will serve as a platform which may hold the key for unveiling the controversial role played by RUNX1 in the context of breast cancer.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:744082 |
| Date | January 2017 |
| Creators | Riggio, Alessandra I. |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/9103/ |
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