Abstract 2501: Proteomics signature of lack of retinoic acid signal surveillance at early breast cancer stages

Abstract

Abstract Endogenous retinoic acid (RA), the bioactive derivative of Vitamin A, is necessary for breast acinar morphogenesis. One of the hallmarks of early stage breast cancer, such as ductal carcinoma in situ (DCIS), is the inability to respond to RA morphogenetic action, which results in the uncontrolled growth of the mammary duct luminal cells. By imaging endogenous RA signaling during normal and aberrant breast acinar development in three dimensional (3D) culture, we found that the inability to form the acinar lumen can be traced to lack of activation of the RA receptor alpha (RARA) genomic function by endogenous RA variation. We further found that aberrant acinar morphogenesis, regardless of the causing factors, is marked by a distinct protein signature, which includes the upregulation of Annexin A8 (ANXA8). Forced expression of ANXA8 in breast epithelial cells was sufficient to disrupt 3D acinar architecture. Moreover, by screening DCIS tissue microarrays (TMAs), we found that ANXA8 expression correlates with tumor grade and stage. Thus, further development of this proteomics signature indicative of lack RA signal surveillance is expected to assist in the early detection of initial breast cancer stages. This work was funded by R01 CA127614, the Friends for an Earlier Breast Cancer Test Foundation, and the Terri Brodeur Breast Cancer Foundation. Citation Format: Stefano Rossetti, Wiam Bshara, Nicoletta Sacchi. Proteomics signature of lack of retinoic acid signal surveillance at early breast cancer stages. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2501. doi:10.1158/1538-7445.AM2014-2501