Abstract B071: PVT1 regulation of claudin expression in triple-negative breast cancer

Abstract

Abstract Breast cancer (BC) is a heterogeneous disease that is classically driven by the estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (EGFR2/HER2) signaling pathways. Triple negative breast cancer (TNBC), is a lethal subtype of invasive BC tumors that are ER-, PR- and HER2-. A subtype of TNBC is claudin low (CL). Dysregulation of claudin proteins disrupts tight junctions, consequently inducing the epithelial-to-mesenchymal transition (EMT) in cancers. This leads to enhanced motility and metastasis. Patients with CL TNBC have worse prognosis than patients with other BC subtypes. African American (AA) women with TNBC account for almost 20% of all BC cases and premenopausal African American (AA) women are more likely to die from the disease. PVT1 is a long noncoding RNA (lncRNA) transcribed from the 8q24 genomic locus that has been implicated in multiple cancers including BC. Amplification of the 8q24 gene locus is a common event in many malignant diseases and is associated with poor survival rate among patients. Although previous research demonstrates a critical functional role which PVT1 plays in BC, the underlying molecular mechanisms of PVT1 in CL TNBC was previously unknown. We assessed PVT1 expression in BC, and we observed that PVT1 exons 4A, 4B, and 9 are significantly upregulated in MDA MB 231 cells (claudin low) and significantly downregulated in MDA MB 468 cells (claudin high), in comparison to T47D (ER+). We have confirmed that claudin expression, specifically claudins 1, 3, 4 and 7, are higher in MDA MB 468 and lower in MDA MB 231. When PVT1 exon 9 expression is silenced in the MDA MB 231 CL TNBC cell line, we observed a significant reduction in migration when compared to cells transfected with a control scramble siRNA, suggesting that PVT1 exon 9 may be regulating migration in CL TNBC. Further investigation could lead to an understanding of the molecular mechanisms by which PVT1 exon 9 regulates claudin expression and consequently clinical outcome in TNBC. Citation Format: Fayola Levine, Olorunseun Ogunwobi. PVT1 regulation of claudin expression in triple-negative breast cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B071.