Investigation of COX2 Regulation of HERV-K in Triple Negative Breast Cancer (360G-Wellcome-206921_Z_17_Z)

HERV-K is the youngest family of human endogenous retroviruses which constitute 8% of our genome. HERV-K is capable of transcribing gag and env proteins, and the spliced accessory proteins Rec and Np9. My supervisor Dr. Sharon Glynn has previously demonstrated the HERV-K env protein is expressed in breast and prostate cancer, and is associated with lymph node metastasis and poor outcome in breast cancer patients. However the molecular mechanisms by which HERV-K is induced and impacts breast cancer progression are unknown. Currently research has established a role for estrogen and progesterone as inducers of HERV-K in breast cancer. However HERV-K is also expressed in hormone receptor negative-triple negative breast cancer. We hypothesise that inflammatory mediators including COX2 may play a role in HERV-K expression in triple negative breast cancer. Objectives: Determine if pro-inflammatory cytokines and prostaglandins are inducers of HERV-K mRNA in triple negative breast cancer. Determine if NSAIDs (e.g. ibuprofen and aspirins) inhibit HERV-K mRNA expression in triple negative breast cancer through inhibition of cyclooxygenase enzymatic activity. Examine the association of COX2 and HERV-K env expression in 20 cases of invasive ductal carcinoma of the triple negative breast cancer subtype, and correlation with pathological features and disease free survival.