Abstract 5348: Transduction of tumors in vivo with choline kinase shRNA downregulates breast cancer stem cell markers

Abstract

Abstract Increased phosphocholine is one of the metabolic signatures of cancer, and is closely associated with malignant transformation, invasion and metastasis. Increased phosphocholine is primarily due to increased expression of choline kinaseα, the enzyme that converts choline to the membrane precursor phosphocholine. Stem-like breast cancer cells (SBCCs) are drug resistant, invasive, and likely to lead to recurrence and repopulation. High CD44 adhesion molecule expression and high expression of the drug transporter ABCG2 are two markers associated with populations enriched with SBCCs [1]. Here we have examined the relationship between choline kinase and these two markers of SBCCs. We have determined the relationship between choline kinase downregulation and two markers of SBCCs, CD44 and ABCG2 in MDA-MB-231 breast cells in vitro and tumors in vivo upon lentiviral transduction of shRNA targeting choline kinase [2]. CD44 and its variant isoforms CD44v6 and CD44v8, together with ABCG2 showed a significant reduction in mRNA (30% for CD44 total; 80% for CDv6 and v8, and 45% for ABCG2) and protein expression levels following transduction of MDA-MB-231 cells with lentivirus expressing shRNA against choline kinase. Similar decreases were also observed following systemic intravenous injections of lentivirus expressing choline kinase shRNA delivered over four weeks. These studies provide insight into potential metabolic targeting of SBCCs. 1. Al-Hajj, M et al., Proc Natl Acad Sci U S A, 2003. 2. Krishnamachary, B et al., Cancer Research, 2009. This work was supported by NIH R01CA136576 and P50 CA103175. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5348. doi:1538-7445.AM2012-5348