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CaArray_green-00030: 2-methoxyestradiol (2ME2) induces mammary gland differentiation through amphiregulin-EGFR mediated signaling

ABSTRACT: 2-methoxyestradiol (2ME2) induces mammary gland differentiation through amphiregulin-EGFR mediated signaling: molecular distinctions from the mammary gland of pregnant mice.High levels of 2ME2 are observed in the late stages of pregnancy. We investigated the role of 2ME2 on normal mammary gland development. Large scale gene expression assays were performed using Affymetrix GeneChips in pursuit of detailed molecular basis. (1) Mammary glands of wild type FVB mice administered 75 or 150 mg/kg of 2ME2 (2) Mammary glands of normal FVB/Nj mice (i) at day 16 of pregnancy, (ii) day 2 of lactation (iii) day 30 of post-lactation, and (3) mammary epithelial SCp2 cells after 6, 24 and 48 hours of 10 micromol 2ME2 treatment were examined. In vivo studies revealed that 2ME2 treatment up regulates the expression of amphiregulin. The clue to the role of 2ME2 in differentiation comes from studies in vitro which detected down regulation of inhibitor of differentiation (Id-1) gene and consequent up regulation of amphiregulin. The differentiation of E2 negative SCp2 cells by 2ME2 indicate estradiol independent mechanism. For details, please see our paper in Endocrinology 2006. **NOTE: Migrated from caArray 1.x, identifier='gov.nih.nci.ncicb.caarray:Experiment:1015897590892008:1'

ORGANISM(S): Mus musculus

PROVIDER: GSE70048 | GEO | 2015/06/20

SECONDARY ACCESSION(S): PRJNA287539

REPOSITORIES: GEO

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Project description:The mammary gland of the lactating mouse synthesizes and secretes milk lipid equivalent to its entire body weight in a single 20 day lactation cycle, making it one of the most active lipid synthetic organs known. To test the hypothesis that multiple metabolic control points and potential regulatory mechanisms are involved in activating lipid and lactose synthesis at the onset of lactation we compared the mammary transcriptome of 130 genes involved in glucose metabolism between late pregnancy and early lactation and in response to dietary fat. We utilized data obtained from microarray analysis of mammary glands from quadruplicate FVB mice at pregnancy day 17, and lactation day 2. Diets containing 8% or 40% lipid were fed from lactation days 5 to 10 and mammary glands and livers of triplicate FVB mice prepared for microarray analysis. We also compared the metabolome obtained from magnetic resonance spectroscopy of flash frozen glands of the mammary gland at day 17 of pregnancy with that at day 2 of lactation. The results provide a global picture of the multiple metabolic strategies utilized to turn a quiescent organ into an incredibly efficient machine for massive but balanced lipid and lactose synthesis and implicate the transcription factor SREBP-1c in regulation of part of the pathway. FVB control time-series mice were on normal lab chow diets and mammary tissue was taken at Pregnant days 12 and 17, plus lactation days 1, 2, and 9 in those animals. the time-points were taken as quadruplicates for each developmental stage. for the dietary component, triplicate FVB dams were fed normal lab chow diets until lactation day 5, when they were converted to diets containing either 8% or 40% Kcal from soy oils (see supplementary table to publication for further detail) for 5 days. At lactation day 10, mammary and liver tissues were taken from these animals and preparred for microarray analysis. All tissues were stabilized for RNA content in RNALater and were then isolated and cleaned up following manufacturer's instructions (Qiagen).

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CaArray_green-00030: 2-methoxyestradiol (2ME2) induces mammary gland differentiation through amphiregulin-EGFR mediated signaling

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