Gene expression signatures relating mammary stem cell populations to breast cancers have focused on adult tissue. pathways impinging on fMaSC growth. Expression profiles from fMaSCs and associated stroma exhibit significant similarities to basal-like and Her2+ intrinsic breast malignancy subtypes. Our results reveal significant links between development and cancer and provide resources to identify new candidates for diagnosis prognosis and therapy. Introduction Breast cancers are a heterogeneous group of diseases distinguishable by histopathology and molecular profiling. Expression profiling of patient samples enabled categorization into molecular subtypes referred to as luminal A luminal B Her2 positive basal-like and claudin-low (Herschkowitz et al. 2007 Perou et al. 2000 These divisions identify critical differences in cellular composition and molecular pathways suggesting treatment options and correlating with patient survival (Prat and Perou 2011 Prognostic expression signatures refined by related approaches are being tested or used clinically (Fan et al. 2011 Paik et al. 2006 van ’t Veer et al. 2002 van de Vijver et al. 2002 Previously reported prognostic signatures and subtype designations identify a limited set of biologic programs correlating with hormone receptor status (Estrogen and Progesterone Receptors ER and PR) Her2 expression and proliferation (Desmedt et al. 2008 Fan et al. 2006 Haibe-Kains et al. 2008 Prat and Perou 2011 Sotiriou and Piccart 2007 While hormone receptors and Her2 are therapeutic targets many breast cancers including most basal-like subtypes lack ER PR and Her2 expression and associated targeted treatment options (Pal et al. 2011 Stem cell biology offers promise for understanding the origins and progression of breast and other cancers and may also reveal the next generation of molecular targets for breast cancers not susceptible to current brokers. For example basal-like breast cancers are poorly differentiated and exhibit gene expression similarities to embryonic and induced pluripotent stem cells (Ben-Porath et al. 2008 Mizuno et al. Flumazenil 2010 Expression profiles derived from adult mammary cells of different differentiation stages have also been Rabbit Polyclonal to TUT1. Flumazenil used to designate cancers as stem like or non-stem like (Lim et al. 2009 Lim et al. 2010 Perou et al. 2010 Breast malignancy cells that generate xenografted tumors with high efficiency regenerate the cellular complexity of the originiating tumor and that self-renew as defined by secondary transplantation exhibit properties attributed to stem cells and have consequently been called breast “malignancy stem cells” (Al-Hajj et al. 2003 However defining potential associations between stem-like cells in breast cancer breast Flumazenil malignancy stem cells and normal mammary stem cells (MaSC) requires MaSC isolation and characterization. Adult MaSCs (aMaSCs) have been enriched using stem cell isolation methods and their gene expression signatures have been reported (Lim et al. 2009 Lim et al. 2010 Pece et al. 2010 Raouf et al. 2008 Shackleton Flumazenil et al. 2006 Stingl et al. 2006 However aMaSC rarity combined with the cellular complexity of the adult gland make purification challenging (Shackleton et al. 2006 Stingl et al. 2006 and co-purifying stroma and differentiated mammary cells complicate elucidation of their core self-renewal and differentiation programs. The developing mammary gland is usually less complex than the adult gland suggesting that it may facilitate stem cell identification and purification. Furthermore while the extensive proliferation migration and invasion Flumazenil required for mammogenesis do not occur in the resting adult mammary gland they do resemble processes mediating breast malignancy progression (Veltmaat et al. 2003 These observations suggest that stem cells present in fetal mammary rudiments (i.e. fMaSCs) might express genes comprising pathways overlooked by analyses focused on the adult mammary gland and Flumazenil that fMaSCs may reveal new targets to aide detection prognosis and treatment of breast cancers. Consistent with this idea gene expression profiling of bulk epithelium from early mammogenesis revealed significant differences with the adult (Wansbury et al. 2011 Importantly this study did not assess whether the profiled cells exhibited stem cell activity so the relevance of these signatures to fMaSCs remains.