ABSTRACT: MYC favors the onset of tumorigenesis by inducing epigenetic reprogramming of mammary epithelial cells towards a stem cell-like state [microarray]
Project description:MYC favors the onset of tumorigenesis by inducing epigenetic reprogramming of mammary epithelial cells towards a stem cell-like state
Project description:MYC favors the onset of tumorigenesis by inducing epigenetic reprogramming of mammary epithelial cells towards a stem cell-like state [ChIP-seq]
Project description:Mouse embryonic stem cells can be maintained in a naive state of pluripotency by culture conditions containing inhibitors of Mek and Gsk3. Myc activity is essential for efficient cellular reprogramming. We genetically addressed the role of c-myc and N-myc in naive ESCs cultured in 2i by inducing the deletion of both genes using CRE-mediated recombination. Our findings show that myc activity controls the biosynthetic and proliferative machines of ESCs without significantly affecting the pluripotency network.
Project description:Using transgenic mouse models of breast cancer, we demonstrate that loss of ShcA signaling within mammary tumors results in extensive CD4+ T cell infiltration, activation and induction of a humoral immune response. Our studies reveal that ShcA signaling during early breast cancer progression is required to establish and maintain an immunosuppressive state that favors tumor growth. Consistent with these transgenic studies, high ShcA levels correlate with poor outcome and reduced CTL infiltration in primary human breast cancers. Conversely, elevated expression of a ShcA-regulated immune signature, generated from ShcA-null mammary tumors, is a predictor of good prognosis in HER2-positive and basal breast cancer patients. These observations define a novel role for ShcA in polarizing the immune response to facilitate tumorigenesis NIC SHC null Tumors vs. pooled MMPV-NIC reference, some replicate dye swaps
Project description:This SuperSeries is composed of the following subset Series: GSE32727: EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [human] GSE32904: EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [mouse] Refer to individual Series
Project description:We used microarrays to futher characterize the effects of T58A mutation in Myc on mammary tumorigenesis. 17 MMTV-Myc T58A mammary tumors were used for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Rank overexpression attenuates mammary tumorigenesis by inducing senescence in mammary epithelial cells but enhances tumor aggressiveness by increasing stemness.
Project description:Basal-like breast cancer is a heterogeneous disease characterised by the expression of basal cell markers, no oestrogen or progesterone receptor expression and a lack of HER2 overexpression. Recent studies have linked activation of the Wnt/beta-catenin pathway to basal-like breast cancer. Transgenic mice expressing N-terminally truncated stabilised beta-catenin in the mammary basal/myoepithelial cell layer (K5deltaNbetacat strain) develop mammary hyperplasias that progress to invasive carcinomas. Histological and microarray analyses of these lesions have revealed their high similarity to a subset of basal-like human breast tumours with squamous differentiation. As in human basal-like carcinomas, the Myc pathway was found to be activated in the mammary lesions of K5deltaNbetacat mice. Mammosphere and transplantation assays showed that a basal cell population with stem/progenitor characteristics was amplified in K5deltaNbetacat mouse preneoplastic glands. Myc deletion from the mammary basal layer of K5deltaNbetacat mice abolished both basal cell regenerative capacity and tumorigenesis. These results show that Myc is essential for beta-catenin-induced stem cell amplification and tumorigenesis and that basal stem/progenitor cells may be at the origin of a subset of basal-like breast tumours.
