ABSTRACT
COSIMA RIEMENSCHNITTER, IVETT TELEKI, VERENA TISCHLER, WENJUN GUO, AND ZSUZSANNA VARGA
12.1 INTRODUCTION
Prognosis for breast cancer has improved continuously during the last decades but it is still one of the most frequent causes of tumor related death in women in the western world. Possible reasons of breast cancer mortality are tumor dormancy after treatment followed by local, regional or distant recurrence. Several factors as hormone receptors, HER2 status, proliferation fraction predicting outcome in preoperative setting were extensively examined in previous studies (Chen et al. 2013; Denkert et al. 2010; Lips et al. 2013; Payne et al. 2008; Teleki et al. 2013; van Nes et al. 2012; Varga et al. 2005; Yoshioka et al. 2013). The role of transcription factors (TF) in breast cancer prognosis has been the subject of some previous studies (Ablett et al. 2012; Cimino-Mathews et al. 2013; Giordano et al. 2012;
Guo et al. 2012; Mego et al. 2012). Slug (SNAI2), a transcriptional repressor, is member of the Snail family of zinc finger proteins and capable to act as a master regulator, altering expression of a number of genes including E-cadherin, a transmembrane protein which plays an important role in cell adhesion (Guo et al. 2012). The role of Slug in cancer developmental processes has been highlighted in several publications (Markiewicz et al. 2012; Mego et al. 2012; van Nes et al. 2012). It has been discovered that Slug is involved in an early developmental phenomenon known as ‘Epithelial to Mesenchymal Transition’ or EMT, which results in the acquisition of an invasive, mesenchymal phenotype by epithelial cells. It has been postulated to play an important role in cancer growth and metastases spreading (Guo et al. 2012). Slug and Sox9 were shown to induce epithelial mesenchymal transition (EMT) and their expression consistently defines mammary stem cell state (Guo et al. 2012). Sox9 and Sox10 are two of the 20 different human Sox genes that also encode family of transcription factors (Chakravarty et al. 2011; Muller et al. 2010; Smalley et al. 2013; Soady & Smalley 2012). In cooperation with Slug, Sox9 can be used to determine the mammary stem cell state (Soady & Smalley 2012). Sox9, a nuclear TF, is often localized in cytoplasm of invasive and metastatic breast cancer (Chakravarty et al. 2011). It has been seen that patients with elevated Sox9 levels in cytoplasm suffer from faster tumor cell proliferation and significantly shorter overall survival (Chakravarty et al. 2011).
