The Significance Of Expression Of ERβ Protein In Breast Cancer And The Corelation With Tamoxifen Resistance

Breast cancer is one of the most common malignant tumors in women. The development of about 50% primary breast cancer is related to estrogen. Therefore, the estrogen receptors play an important role in the genesis, growth and therapy of breast cancer. It is believed that the finding of estrogen receptor beta will explain many problems which are unsolved in the field of endocrine therapy. The relationship between tamoxifen resistance and the expression of estrogen receptor beta is unclear and there are contrary results reported in different papers. In order to recognize the clinical significance of estrogen receptor beta we investgate the expression of estrogen receptor beta and its relationship with other prognosis factors in breast cancer, and then explore the correlation betweem estrogen receptor beta and tamoxifen resistance by clinical and laboratory study.1. Association between ERβExpression and the clinical pathology, and Other Prognostic BiomarkersObjective To study the association between ERβexpression and the expression of clinical pathology and other prognostic biomarkers. Methods The expression of ERβ,ER,PR,Ki-67,HER-2/neu and p53 were detected in 109 patients'samples by immunohistochemistry on tissue microarray slides. Morphological parameters of the 109 cases were reviewed. Results ERβwas expressed in 62.6 % of different histologic types of breast cancer. There was a statistically significant association between expression of ERβand TNM staging. No statistically significant association was seen between ERβexpression and age,tumor size and lymphy node status. A inverse correlation was found between expression of ERβand Ki-67. Conclusions ERβappears to be an protective factor in the carcinogenesis of breast cancer and probably an important prognostic marker and therapeutic target. 2. clinical research on the relationship of estrogen receptor-beta and its isoform expression to tamoxifen resistance in human breast cancerObjective To study the relationship of estrogen receptor-beta and its isoform expression to tamoxifen resistance in human breast cancer. Methods Case-control studies were performed with 13 cases of primary breast cancer patient whose disease progressed while on tamoxifen therapy (tamoxifen resistant) and 13 cases of primary breast cancer patient who later had no disease progression (tamoxifen sensitive) . The expression of total estrogen receptor beta(ERβ),ERβ1 and ERβcx were tested by IHC in the cases. Results High total ERβprotein expressers were more frequently observed in tamoxifen sensitive tumors than resistant tumors (P<0.05). However, no significant differences in the relative expression of ERβ1 and ERβcx protein in the tamoxifen sensitive and resistant groups were found. Conclusions The expression of ERβprotein and its isoforms may differ in breast cancer patients who have differential sensitivity to tamoxifen therapy.3. Empirical study on the relationship between ERβexpression to tamoxifen resistance in MCF-7 human breast cancer cellsObjective To study the effects of exogenous ERβon the growth of breast cancer MCF-7 cells under different treatment with estrogen or tamoxifen. Methods An eukaryotic expression vector containing human entire coding sequence of ERβ(pBI-EGFPERβ) was transfected into human breast cancer MCF-7 cells using lipofectin reagent. The biological activity of ERβwas detected with the expression of ERβprotein by Western blot. The growth properties of MCF-7, transfected MCF-7 cells under different treatment, including E2 (17beta-estradiol) and tamoxifen, were observed. Results Western blot analysis showed that the protein level of ERβin the transfected MCF-7 cells was markedly increased. Exogenous ERβexpression inhibit the growth properties of MCF-7 cells under normal condition. The transfected MCF-7 cells proliferated at the same rate as naive cells in the presence of tamoxifen, whereas a strong inhibition of the proliferation of the transfected MCF-7 cells in the presence of E2 was observed. Conclusions Exogenous ERβexpression does not increase the resistance to tamoxifen, and a strong inhibition of the proliferation may occurre in the presence of E2.