Back to top anchor

Oestrogen-dependent regulation of gene expression by cohesin in breast cancer

30 months
Approved budget:
Professor Julia Horsfield
Health issue:
Cancer (oncology)
Proposal type:
International Investment Opportunity
Lay summary
Breast cancer is one of the most common cancers in women worldwide. About 70% of breast cancers are positive for oestrogen receptor alpha (ER) and are dependent on oestrogen for proliferation. ER -positive breast cancers are treated with anti-oestrogens such as tamoxifen, but resistance to anti-oestrogens is common. Understanding the action of oestrogen is essential for developing new therapies. Cohesin is a multi-unit protein involved in both cell division and gene expression. Importantly, cohesin colocalizes with ER on chromosomes, and controls expression of the oestrogen-responsive cancer-causing gene, c-MYC. Since c-MYC overexpression causes resistance to anti-oestrogen therapy, targeting cohesin could overcome endocrine resistance in breast cancer. We will determine how cohesin contributes to genome organisation by ER and identify specific cancer-causing genes that are regulated by both ER and cohesin. We will focus on c-MYC in particular. We expect to identify new pathways for future therapy in ER -positive breast cancers.