Distinct expression patterns of ER alpha and ER beta in normal human mammary gland

AIM: Two oestrogen receptors (ERs) have been identified to date—the “classic” ERa and the more recently described ERb. Although much is known about ERa at the mRNA and protein levels, our knowledge of the expression and distribution of ERb protein is much more limited. The aim of this study was to compare the cellular distribution of ERa and ERb in normal human mammary gland. METHODS: Formalin fixed, paraffin wax embedded material was obtained from reduction mammoplasty specimens, normal tissue adjacent to breast tumour, or fibroadenoma. Sections were immunohistochemically stained for ERa, ERb, and the progesterone receptor. The staining pattern for each antibody was evaluated and compared. RESULTS: ERa was restricted to the cell nuclei of epithelial cells lining ducts and lobules. Although ERb was also seen in these cells, additional strong staining was detected specifically in the cell nuclei of myoepithelial cells. Occasional staining was seen in surrounding stromal and endothelial cell nuclei and in lymphocytes. CONCLUSIONS: ER subtypes have distinct distribution patterns in the normal mammary gland. The widespread distribution of ERb suggests that it may be the dominant ER in the mammary gland where it may be acting as a natural suppressor

Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion

The CUB and sushi multiple domains 1 (CSMD1) gene maps to chromosome 8p23, a region deleted in many cancers. Loss of CSMD1 expression is associated with poor prognosis in breast cancer suggesting that it acts as a tumour suppressor in this cancer. However, the function of CSMD1 is largely unknown. Herein, we investigated CSMD1 functions in cell line models. CSMD1 expression was suppressed in MCF10A and LNCaP cells using short hairpin RNA. Functional assays were performed focusing on the 'normal' MCF10A cell line. Suppression of CSMD1 significantly increased the proliferation, cell migration and invasiveness of MCF10A cells compared to shcontrols. shCSMD1 cells also showed significantly reduced adhesion to Matrigel and fibronectin. In a three-dimensional Matrigel model of MCF10A cells, reduced CSMD1 expression resulted in the development of larger and more poorly differentiated breast acini-like structures that displayed impaired lumen formation. Loss of CSMD1 expression disrupts a model of mammary duct formation while enhancing proliferation, migration and invasion. Our data suggest that CSMD1 is involved in the suppression of a transformed phenotype