Abstract 779: Functional role of TGF-beta receptor type-2 in breast cancer progression and survival

Abstract

Abstract Background and Rational: Transforming growth factor β (TGFβ) signaling is pivotal in cellular proliferation and can exhibit either tumor-suppressive or promoting effects depending on cellular context and genetic alterations. TGFβ receptor type-2 (TGFβR2), the ligand-binding receptor, is implicated in various cancers. This study explores the functional role of TGFβR2 in breast cancer (BrCa) progression. Materials and Method: Genomic alterations in TGFβR2 were assessed in TCGA samples. TGFβR2 mRNA and protein expression were examined in a panel of BrCa cell lines, including MCF7, MCF12A, MDA-MB-231, and MDA-MB-468. Additionally, serum samples from BrCa patients, meticulously categorized into subtypes such as triple-negative (TN), human epidermal growth factor receptor 2-positive (Her2+), Luminal A (LA), Luminal B1 (LB1), and Luminal B2 (LB2), were analyzed. BrCa cell lines were treated with TGFβ ligand to investigate receptor expression modulation. Results: Analysis of genomic alterations in TGFβR2 from The Cancer Genome Atlas (TCGA, n=1084, BrCa samples) revealed TGFβ copy number amplification in 25% of samples, while less than 1% showed TGFβR2 amplification. Elevated TGFβR2 levels were identified in aggressive triple-negative MDA-MB-231 cells compared to other tested cell lines. Serum samples from BrCa patients (n=240) demonstrated higher TGFβR2 levels, particularly in Luminal B1 subtype and African American patients. Treatment of BrCa cell lines with TGFβ ligand induced TGFβR2 expression, suggesting ligand-induced receptor upregulation. Discussion: The findings suggest TGFβR2 as a potential biomarker for BrCa, with higher levels associated with aggressiveness and racial disparities. Ligand-induced receptor upregulation implies a potential oncogenic role. These results contribute to understanding TGFβR2's functional significance and its implications in breast cancer progression, offering insights into potential biomarkers and therapeutic targets. Citation Format: Meera Srivastava, Alakesh Bera, Harvey B. Pollard, Hai Hu, Craig D. Shriver. Functional role of TGF-beta receptor type-2 in breast cancer progression and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 779.