Mapping the effect of estrogen in DARPP-32 aberrant breast cancer
Sarah Storr, University of Nottingham
Breast cancer is the most common cancer in the UK, with >55,000 new cases per annum and >11,500 deaths, with metastasis the major cause of mortality. The molecular basis that underpins metastasis is complex and presents an important research challenge. Around 70% of breast cancers are oestrogen receptor (ER) positive, which allows them to use oestrogen to fuel their growth; this can be targeted by drugs like tamoxifen and anastrazole. Despite these additional treatment options, late recurrence of ER positive breast cancer is a significant problem.
We have identified that in ER positive breast cancer, loss of an important signalling protein, DARPP-32, is associated with shorter survival of patients. Despite this finding, we do not know how low DARPP-32 in the context of ER signalling and receptor status would alter patient survival. This proposal will begin to address this by mapping the changes that occur in a ER positive breast cancer cell line that has been genetically edited to knockout DARPP-32 expression. The cell line will be supplemented with and without estradiol and subject to RNA-Seq. This will provide important insights into how this signalling protein can be co-opted in breast cancer, and provide new opportunities for therapeutic targeting.
Grant awarded: £5,000.00