Abstract 329: Understanding the role of GPR30 in the estrogen non-genomic signaling in inflammatory breast cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2022-06, Vol.82 (12_Supplement), p.329-329
• Main Authors: Soto, Xavier S. Bittman, Lopez, Adrian J. Rivera, Peterson, Esther A.
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2022-329

Inflammatory Breast Cancer (IBC) is rare and the most aggressive subtype of all breast cancers, reporting rapid progression, poor prognosis, and a unique clinical diagnosis (blockage of lymph vessels by tumor emboli). Approximately, 40% of IBC cases are classified as triple-negative breast cancer (TNBC), meaning they test negative for hormone receptors (estrogen and progesterone) and the amplification of the epidermal growth factor receptor 2 (HER2), which leads to no effective targeted therapies availability. However, 17β-estrogen (E2) has been found to enhance the migration and invasion phenotypes of TN-IBC cells and it has been associated with the presence of a membrane G-protein coupled estrogen receptor (GPR30) and a novel cytoplasmic estrogen receptor (ERα36 isoform) that can undergo an estrogen non-genomic (rapid) cell’s response. Recent studies have also reported a crosstalk between these estrogen non-genomic receptors and the epidermal growth factor receptor (EGFR) signaling pathway in the presence of E2, inducing phosphorylation of the extracellular signal-regulated kinase (ERK1/2) and promoting oncogenic phenotypes (migration & invasion) in TN-IBC cells. However, the exact role of GPR30 and ERα36 in the non-genomic signaling pathway remains elusive in TN-IBC. We hypothesis that GPR30 and ERα36 are necessary to undergo de estrogen non-genomic signaling and promote oncogenic phenotypes in TN-IBC SUM149 cells after E2 treatment. Methods: We have measured migratory activity and tumor emboli formation of SUM149 cells (by wound-healing and 3D-cell proliferation assay), and phosphorylation levels of ERK1/2 and AKT kinases (by western-blot) after treatments in time-points with E2 alone and in combination with G15 (GPR30 antagonist drug). We are also working to identify protein partners of GPR30 (by Ip and Mass-spec) after E2 treatment, including physical interaction with ERα36, in TN-IBC and other types of breast cancers. Results: G15 treatment in Sum149 cells significantly reduced E2-induced ERK1/2 phosphorylation, indicating that GPR30 is necessary for the estrogen non-genomic signaling pathway and has direct involvement with the EGFR signaling cascade. Data acquired from these experiments will contribute to a better understanding of TN-IBC’s molecular structure and create new opportunities to develop novel targeted therapies. Citation Format: Xavier S. Bittman Soto, Adrian J. Rivera Lopez, Esther A. Peterson. Understanding the role of GPR30 in the es