Abstract PO2-27-08: Discovery of glucocorticoid receptor-induced EMT and integrin gene expression and increased cell motility in invasive lobular breast cancer

Abstract

Abstract Estrogen receptor (ER)-positive, invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer. Although the five-year stage-matched survival is improved compared to infiltrating ductal carcinoma (IDC), ILC late metastatic recurrences ( >5 years) are more frequent. Understanding the molecular mechanisms of lobular breast cancer’s significantly dormant yet ultimately metastatic phenotype is important to improve clinical outcomes. Our laboratory had previously shown that GR activation in ER+ IDC was associated with decreased cell proliferation, but little is known about GR activity in ER+ ILC. By examining gene expression following GR activation in metastases-derived ER+/GR+ human ILC cell lines, we recently uncovered that GR-activation increases EMT and integrin pathways. Here we show for the first time that in addition to activation of these gene expression pathways, GR activation increases ILC cellular migration in microchannels coated with collagen and fibronectin, consistent with a potential for GR activation to increase ILC metastases. We examined GR expression and activation in SUM44 GR+/GR-, and BCK4 GR+/GR- and MM134 GR+ cell lines and will present data comparing gene GR- mediated expression in the presence of cortisol and clinically relevant GR modulation. Ongoing investigations also include in vivo MIND modeling with GR modulation. Citation Format: Baylee Porter, Candace Frerich, Muriel Laine, Sunati Sahoo, Geoffrey Greene, Jeon Lee, Lynda Bennett, Suzanne Conzen. Discovery of glucocorticoid receptor-induced EMT and integrin gene expression and increased cell motility in invasive lobular breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-08.