%0 Journal Article
%T ER¦Â in normal and malignant breast
%A J-£¿ Gustafsson
%A G Cheng
%A M Warner
%J Breast Cancer Research
%D 2005
%I BioMed Central
%R 10.1186/bcr1054
%X We have shown that in the rodent mammary gland ER¦Â is the dominant ER, and that, in response to E2, ER¦Á but not ER¦Â is downregulated in the early G1 phase of the cell cycle. Cells that contain ER¦Á receive the signal to proliferate from E2, and within 4 hours of that signal ER¦Á is lost from the nucleus. The cells then go through a complete cycle and ER¦Á reappears in daughter cells. ER¦Â levels do not change in cell nuclei during the cell cycle. This pattern of ER regulation holds true in human breast cancer since ER¦Á is never co-localized with proliferation markers in breast cancer samples. This means that under the conditions of a constant high level of E2, ER¦Á does not reappear in the nucleus. A similar situation exists during pregnancy when there is a constant high level of E2 and there is no ER¦Á in the mammary epithelium. This resistance to the proliferative response to E2 in the presence of a constant high dose of E2 probably explains the very successful use of high-dose E2 in the treatment of breast cancer. ER¦Â, on the other hand, appears to have a differentiative role not a proliferative role in the mammary gland, and the lactating rodent mammary gland of ER¦Â-/- mice does not express gap junction and adhesion proteins, typical indicators of fully differentiated cells.In recent years there have been several publications showing that ER¦Â is expressed in human breast cancer, and conclusions and speculations about a causative role for ER¦Â in breast cancer development and/or progression have been made. We have studied 500 frozen breast biopsies in collaboration with Prof. RC Coombes, London, in order to clarify the role of ER¦Â in normal and malignant breast. In this study we measured ER¦Á and ER¦Â proteins by several techniques (immunohistochemistry, western blotting, ligand binding in sucrose gradients, and RT-PCR) in various human samples obtained from both benign breast and malignant breast. We found that ER¦Â is the predominant estrogen receptor in the normal mamma
%U http://breast-cancer-research.com/content/7/S2/S.11