%0 Journal Article
%T Estrogen receptor ¦Â represses Akt signaling in breast cancer cells via downregulation of HER2/HER3 and upregulation of PTEN: implications for tamoxifen sensitivity
%A Karolina Lindberg
%A Luisa A Helguero
%A Yoko Omoto
%A Jan-£¿ke Gustafsson
%A Lars-Arne Haldos¨¦n
%J Breast Cancer Research
%D 2011
%I BioMed Central
%R 10.1186/bcr2865
%X T47-D and MCF-7 ER¦Á-expressing breast cancer cells with tetracycline-regulated expression of ER¦Â were used as a model system. Expression levels and activity of known regulators of endocrine resistance were analyzed by performing quantitative polymerase chain reaction assays, Western blot analysis and immunostaining, and sensitivity to tamoxifen was investigated by using a cell proliferation kit.Expression of ER¦Â in ER¦Á-positive T47-D and MCF-7 human breast cancer cells resulted in a decrease in Akt signaling. The active form of an upstream regulator of Akt, proto-oncogene c-ErbB-2/receptor tyrosine kinase erbB-3 (HER2/HER3) receptor dimer, was also downregulated by ER¦Â. Furthermore, ER¦Â increased expression of the important inhibitor of Akt, phosphatase and tensin homologue deleted on chromosome 10 (PTEN). Importantly, ER¦Â expression increased the sensitivity of these breast cancer cells to tamoxifen.Our results suggest a link between expression of ER¦Â and endocrine sensitivity by increasing PTEN levels and decreasing HER2/HER3 signaling, thereby reducing Akt signaling with subsequent effects on proliferation, survival and tamoxifen sensitivity of breast cancer cells. This study supports initiatives to further investigate whether ER¦Â presence in breast cancer samples is an indicator for endocrine response. Current therapies in ER¦Á-positive breast cancers aim to impair ER¦Á activity with antagonists or by removal of endogenous estrogens with aromatase inhibitors. Data from this study could be taken as indicative for also using ER¦Â as a target in selected groups of breast cancer.Approximately two-thirds of breast cancers express estrogen receptors (ERs) and initially require estrogen to grow, and are therefore treated with ER antagonists, such as tamoxifen, or by depletion of endogenous estrogens with aromatase inhibitors [1,2]. Two ERs, ER¦Á and ER¦Â, have been identified [3]. ER¦Á plays an important role in the proliferation and progression of breast cancer, whereas a d
%U http://breast-cancer-research.com/content/13/2/R43