Abstract B136: Sox10 expression labels in vitro mammary stem cell activity

Abstract

Abstract Molecular pathways that guide cell proliferation and programming events during embryonic development to generate specific organs may be aberrantly re-activated in the cancer state of those organs to drive tumor progression. Recently, our laboratory has successfully demonstrated the applicability of this tenet to studies of breast cancer. We have developed an enrichment protocol for fetal mammary stem cells (fMaSCs) from embryonic mammary rudiments, and verified that particular subtypes of breast cancers, including Basal-like triple-negative breast cancers for which targeted therapies do not exist, show strong correlation with expression signatures found in fMaSCs. This suggests that elucidation of the biology behind fMaSC function will yield important insight into better treatment of these aggressive breast cancers. To identify mechanisms that govern fMaSC function, we have performed transcriptome analyses on cell populations enriched for fMaSCs and their surrounding stroma. From this data, we have identified candidate signaling and transcription networks that we are currently validating. Here we describe ongoing work with one candidate to emerge from our analyses, Sox10. Sox10 is specifically expressed in the enriched fMaSC population, and is of particular interest given the well-documented roles for other Sox family transcription factors in: 1) regulating cell fate decisions in embryonic and adult tissue, and 2) mediating the progression of some types of cancer. We show that Sox10 expression specifically correlates with MaSC function in fetal and adult mammary. We further show that Sox10 expression can be utilized to identify the cells maintaining MaSC stem cell properties in culture. Importantly, incorporation of Sox10 into our existing fMaSC purification protocol results in a twofold improvement in fMaSC enrichment. Our discoveries with Sox10 thus represent a molecular focal point around which to build signaling and transcriptional networks underlying fMaSC state and function. They further demonstrate the promise of our approach in identifying novel targets for the development of new therapies for poorly treated cancers. Citation Format: Christopher Dravis, Claire Johns, Benjamin T. Spike, Michelle Southard Smith, Geoffrey M. Wahl. Sox10 expression labels in vitro mammary stem cell activity. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B136.