Project description:The mammary epithelia are mainly composed of two distinct lineages, the basal and luminal cells. In our MMTV-Cre; Brca1flox/flox mouse model, we found the Brca1 knockout mainly occurred in the luminal cells, which will lead the mammary tumorigenesis. To investigate the Brca1 deficiency mediated mammary tumorigenesis, we sorted the luminal cells from wild type mice and MMTV-Cre; Brca1flox/flox mice for RNAseq analysis.
Project description:Mammary stem and progenitor cells are essential for mammary gland homeostasis and are also candidates for cells of origin of mammary tumors. Here, we provide evidence that the protein kinase p38a is required for the differentiation of luminal progenitor cells through modulation of the transcription factors Runx1 and Foxa1. Moreover, using a mouse model for breast cancer initiated by luminal cells, we show that p38a downregulation in mammary epithelial cells reduces tumorigenesis, which correlates with reduced numbers of tumor-initiating cells. Our results identify p38a as a key regulator of luminal progenitor cell fate that facilitates mammary tumor formation.
Project description:The aim of this project is to examine age-dependent changes in the proteomes and phosphoproteomes of normal human mammary luminal epithelial and myoepithelial cells.
Project description:We have identified GATA-3 as a critical regulator of luminal cell differentiation in the mammary gland. Acute loss of GATA-3 in the adult mammary gland leads to an expansion of an undifferentiated luminal epithelium and the formation of a multi-layered epithelium. Here we report microarray analysis of mammary glands that have undergone acute loss of GATA-3 Keywords: genetic modification
Project description:We used a mouse strain in which one Tbx3 gene was replaced with the yellow fluorescent protein variant Venus. Luminal cells had either very high Tbx3 promoter activity or not at all. We performed an expression analysis on luminal mammary epithelial cells sorted based on their Venus expression (reporting Tbx3 promoter activity) to investigate the difference between these two cell populations. Mammary epithelial cells from 3 Tbx3-Venus-KI adult virgin female mice (FVB background) were pooled and luminal cells were sorted into a Venus-hi and a Venus-neg sample. There were no repeats for this study.
Project description:We report here the transcriptional signature of Notch1-expressing (GFP positive) luminal mammary progenitors compared to total luminal cells (GFP negative). For each condition, 3 biological replicates were performed, by pooling the mammary glands from two mice/replicate.
Project description:To identify genes specifically expressed in lactating mammary glands, the gene expression profiles of luminal and basal cells from different developmental stages were compared. Comparison of gene expression in luminal and basal cells harvested from the mammary glands of virgin, 18.5 day pregnant and 2 day lactating mice (2 mice per stage).
Project description:LSD1 (KDM1A) is a histone demethylase that plays both oncogenic and tumor suppressor roles in breast cancer. However, the exact contexts under which it plays these opposite roles remain largely elusive. By characterizing its role in normal and cancerous luminal mammary epithelial cells (MECs), here we show that LSD1 is essential for maintaining differentiation and survival of luminal cells. LSD1-inhibition by both genetic and pharmacological approaches increases invasion of luminal breast cancer cells. Mechanistically, we find LSD1 interacts with GATA3 and their common target genes are highly related to breast cancer. LSD1 positively regulates GATA3 expression and represses that of TRIM37, a histone H2A ubiquitin ligase and breast cancer oncoprotein. LSD1-loss leads to reduced expression of several cell junction genes (e.g., CDH1, VCL, CTNNA1), possibly via TRIM37-mediated repression. Collectively, our data suggest LSD1 largely plays a tumor suppressor role in luminal breast cancer and the increased MEC invasiveness associated with LSD1-inhibition can be blocked via TRIM37-inhibition.