Abstract A130: Progesterone expands a hormone-dependent progenitor population in luminal breast cancers

Abstract

Abstract More women die of Luminal, hormone-dependent, breast cancers than any other types. These tumors are estrogen (ER) and progesterone (PR) receptor-positive. Luminal cancers can recur many years after diagnosis, and when they do, they are just as deadly as rapidly-recurrent Basal cancers. Cytokeratin 5 (CK5) is a marker of triple negative Basal breast cancers. We have models in which Luminal breast cancer cells grown as xenografts in ovx'd mice or as 3D colonies in hormone-free or estrogen (E)-containing media are ER+PR+CK5–. However, if E is supplemented with progesterone (P), an ER–PR–CK5+ Basal-like subpopulation expands; we term these cells “Luminobasal”. Detailed IHC shows heterogeneity within the E+P-induced Luminobasal population, with rare cells that are ER+PR+CK5+; hence “Double Positive”. Similar “Double Positive” cells can be detected in clinical Luminal tumor samples stained for PR and CK5. Luminal cells in E+P colonies were FACS-sorted into CK5+ and CK5– subpopulations. RNA was extracted and subjected to gene expression profiling. The gene list was analyzed for cell surface markers unique to the CK5+ cells that might be useful for live-cell FACS sorting. Several were tested, and one marker is of considerable interest. FACS analysis shows that these Double Positive cells are rare (0.12%) in E, but increase to 6.63% under E+P. The cells are confirmed PR+CK5+ by IHC. Importantly, these PR+CK5+ cells form mammospheres indicating their self-renewal capacity. In the absence of hormones, the cells within the mammospheres differentiate into the heterogenous subpopulations that characterize Luminal disease, including PR+CK5–, PR–CK5+ and PR+CK5+ cells. Studies of hormone dependence and tumor-forming potential are ongoing. We speculate that Double Positive cells are progenitors of Luminal tumor-cell heterogeneity. Citation Format: Huaping Fan, Kathryn B. Horwitz. Progesterone expands a hormone-dependent progenitor population in luminal breast cancers. [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 A130.