102P - Functional characterization of mammagliobin-1 isoform in breast cancer

Abstract

Background: Since 2007, oncologists have been using the GeneSearchTM Breast Lymph Node (BLN) Assay for the detection of metastatic breast cancer. This test detects the presence of Mammaglobin-1 (MGB1) expression in lymph nodes of breast cancer patients. Although MGB1 is overexpressed in 90% of breast cancers, its aberrant expression and function in breast cancer tissue is still misunderstood. We have recently reported the first evidence for MGB1 as potent induction of breast cancer malignancy and disease progression. More precisely, loss of MGB1 expression correlates with a decrease of cell proliferation, spheroid formation, migration, and invasion capacities of breast cancer cells. Concomitantly, we also show that MGB1 expression activates pro-malignant signaling cascades leading to epithelial to mesenchymal transitioning (EMT). More interestingly, we have also discovered new MGB1 gene products that result from transcript editing. The objective of this research is to elucidate the role of MGB1 gene products in breast cancer, we set out to investigate and characterize MGB1 isoforms in breast cancer cell processes. Methods: MGB1 isoforms were identified by 3’and 5’-RACE assays and next generation sequencing using the minion platform. The novel MGB1 gene products were subsequently cloned. Results: In total, we have identified 7 different MGB1 product variants. We strongly believe that each MGB1 product has a specific cellular role, which leads to breast cancer malignancy and disease progression. To perform loss and gain of function experiments, we are genetic engineering breast cancer models that specifically code and express individual MGB1 variants with and without tracking epitope tags. Conclusions: This study will elucidate the molecular and cellular mechanism leading to breast cancer progression. MGB1 variants may provide new avenues for therapeutic or prognostic strategies. Legal entity responsible for the study: N/A Funding: Mitacs Globalink, Baxter and Alma Ricard, Canadian Institute of Health Research, Beatrice Hunter Cancer Research Institute, New Brunswick Health Research Institute, O'Brien Foundation, Canadian Breast Cancer Foundation, Atlantic Canada Opportunities Agency, Université de Moncton Campus Moncton Disclosure: All authors have declared no conflicts of interest.