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    Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue.

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    Authors
    Wilson, Claire L
    Sims, Andrew H
    Howell, Anthony
    Miller, Crispin J
    Clarke, Robert B
    Affiliation
    Cancer Research UK Bioinformatics Group, Paterson Institute for Cancer Research, Wilmslow Road, Withington, Manchester M20 4BX, UK.
    Issue Date
    2006-06
    
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    Abstract
    Oestrogen (E) is essential for normal and cancer development in the breast, while anti-oestrogens have been shown to reduce the risk of the disease. However, little is known about the effect of E on gene expression in the normal human breast, particularly when the epithelium and stroma are intact. Previous expression profiles of the response to E have been performed on tumour cell lines, in the absence of stroma. We investigated gene expression in normal human breast tissue transplanted into 9-10-week-old female athymic nude (Balb/c nu/nu) mice. After 2 weeks, when epithelial proliferation is minimal, one-third of the mice were treated with 17beta-oestradiol (E2) to give human luteal-phase levels in the mouse, which we have previously shown to induce maximal epithelial cell proliferation. RNA was isolated from treated and untreated mice, labelled and hybridized to Affymetrix HG-U133A (human) GeneChips. Gene expression levels were generated using BioConductor implementations of the RMA and MAS5 algorithms. E2 treatment was found to represent the largest source of variation in gene expression and cross-species hybridization of mouse RNA from xenograft samples was demonstrated to be negligible. Known E2-responsive genes (such as TFF1 and AREG), and genes thought to be involved in breast cancer metastasis (including mammoglobin, KRT19 and AGR2), were upregulated in response to E treatment. Genes known to be co-expressed with E receptor alpha in breast cancer cell lines and tumours were both upregulated (XBP-1 and GREB1) and downregulated (RARRES1 and GATA3). In addition, genes that are normally expressed in the myoepithelium and extracellular matrix that maintain the tissue microenvironment were also differentially expressed. This suggests that the response to oestrogen in normal breast is highly dependent upon epithelial-stromal/myoepithelial interactions which maintain the tissue microenvironment during epithelial cell proliferation.
    Citation
    Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue. 2006, 13 (2):617-28 Endocr. Relat. Cancer
    Journal
    Endocrine-Related Cancer
    URI
    http://hdl.handle.net/10541/72735
    DOI
    10.1677/erc.1.01165
    PubMed ID
    16728587
    Type
    Article
    Language
    en
    ISSN
    1351-0088
    ae974a485f413a2113503eed53cd6c53
    10.1677/erc.1.01165
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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