Mammary Gland Tumor Development in Transgenic Mice Overexpressing Different Isoforms of the CDP/Cux Transcription Factor

摘要

Short CUX1 isoforms were found to be overexpressed in breast cancer cell lines, in human breast tumors and in uterine leiomyomas, suggesting that these proteins play a key role in tumor development and progression. My project consisted in analyzing the effect of these CUX1 isoforms on mammary gland development and tumorigenesis. Also, I worked on the identification of targets of CUX1 mediating its oncogenic properties. So far, I have shown that overexpressing short CDP/Cux isoforms leads to abnormal development of the mammary gland. Furthermore, overexpressing p75, p110 or p200 CDP/Cux leads to the development of mammary gland tumors in mice. These tumors seem to be of basal origin, suggesting that CUX1 promotes tumorigenesis in a precursor cell. Breast tumor patients with similar types of disease have very low chances of survival, since no specific treatment is currently available for them. Thus, my research project will enable us to gain a better understanding of the biological functions of each CUX1 isoform in mammary gland development and tumorigenesis, which could possibly lead to new therapeutic targets for the treatment of basal breast cancers.