Abstract 6726: Investigating the tumor suppressive role of LRIG1 in breast cancer disparities
Authors: Amber Yu, Angel H. Pajimola, Kayla S. Ingram, Brittany Jenkins-Lord
Journal: Cancer Research (2025)

Abstract Background: Within the U.S. population, African American (AA) women have a staggering 40% higher mortality rate from breast cancer than European American (EA) women, despite having a lower incidence rate. This disproportionate mortality burden imposed on AA women is rooted in both environmental and genetic causes. We are interested in elucidating molecular and environmental mechanisms that may be contributing to these breast cancer health disparities. Our recent study identified that higher neighborhood-level socioeconomic deprivation was associated with hypomethylation and decreased gene expression for LRIG1 (Leucine-rich repeats and immunoglobulin-like domains 1) in AA women, but not in EA women. LRIG1 has been shown to act as a tumor suppressor, associating with members of the ErbB family of receptor tyrosine kinases (RTKs), which includes the epidermal growth factor receptor (EGFR), HER2, HER3, and HER4. This association of LRIG1 with ErbBs is predicted to result in the degradation of these proteins and the suppression of pro-growth signaling. Objective: This project aims to determine differences in the protein expression of LRIG1 and ErbB proteins within breast epithelial cell lines (normal epithelial cells, estrogen receptor-positive (ER+), and estrogen receptor-negative (ER-)) derived from both AA and EA women. We hypothesize that there are differences in the protein expression of LRIG1 and ErbB proteins within breast epithelial cell lines derived from AA women and EA women. Methods: The levels of protein expression of LRIG1 and ErbB proteins in the cell lines were assessed using Western immunoblotting and densitometric analysis. The colocalization of LRIG1/EGFR and LRIG1/HER2 in non-tumorigenic, ER+, and ER- cell lines was assessed through immunofluorescence (IF) cell staining. Results: Western immunoblotting revealed substantial variation in target protein levels, with notable differences in LRIG1 protein levels by estrogen receptor status, with greater LRIG1 protein expression in ER+ cell lines. IF staining demonstrated limited colocalization between LRIG1 and EGFR as well as LRIG1 and HER2. Future experiments, including co-immunoprecipitation, will aim to determine how LRIG1 and the ErbB proteins are interacting and what factors may be influencing their binding and downstream signaling. Conclusions: Our results provide insight into LRIG1 and ErbB co-expression in several breast cell lines from AA and EA women. Our next steps will include identifying distinct differences between these cell lines that might be a result of variations in environmental factors, the tumor microenvironment, and genetic ancestry. Citation Format: Amber Yu, Angel H. Pajimola, Kayla S. Ingram, Brittany Jenkins-Lord. Investigating the tumor suppressive role of LRIG1 in breast cancer disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6726.