Estrogen Receptor (er¦Á) Expression Pattern And Regulatory Proteins

Estrogen receptor (ERa) is a member of a large superfamily of nuclear receptors that regulate the transcription of estrogen-responsive genes. ERa is an effective treatment target as well as a prognostic factor of breast cancer. Recently, endocrine therapy of breast cancer is acquired mainly by decreasing ERa transcriptional activity. The objective of the current study was to investigate the expression regularity and the clinicopathological characteristics of ERa in Chinese female patients with breast cancer, to explore the relationship between ERa and other molecular markers, do some analytical study about partial function of the NFAT3 to investigate the biological characteristics of breast cancer, and ultimately provide reasonable evidence-based medical verification for treatment of breast cancer. In first part of clinical study, a retrospective study was done to reveal the expression regularity of ERa in 2080 Chinese female patients with breast cancer. We found that the whole positive rate of ER a was 53.6% , and the positive rate by DCC (1169 cases) and IHC (911 cases) was 50.6% and 57.4%, respectively. ERa was correlated significantly with smaller tumour size(P=0.019), positive PgR(P<0.0005) and Bcl2(P<0.0005), negative HER2(P<0.0005). ERa expression was not associated with age, menopause, clinical stage, axillary node metastasis, lesions and pathological type of the tumour.lt is coincident between estrogen receptor status in the primary tumor and its regional and distant metastases. Univariate and multivariate analysis were performed using chi squared test, log-rank test and Cox's regression model. ER a had a significantly better 5-year disease-free survival (DPS) and overall survival (OS) in univariate analysis. However, in a multivariate analysis, ER a and clinical stage were significant predictors for both 5-year DPS and OS.In second part, our studies concentrate on the role of NFAT3 in breast cancer cells. These studies indicated that NFAT3 may interact with ERa and enhanced ERa-dependent transcriptional activity and pS2 transcription in a ligand-independent manner, suggesting that NFAT3 is a novel ERa coactivator. A MCF-7 cell line was constructed to express NFAT3 stably. RT-PCR analysis indicated that compared toempty vector, overexpression of NFAT3 could elevate the expression of some estrogen-regulated genes such as pS2, CathD, and Bcl2. These findings suggest that NFAT3 may directly modulate ERa signaling. Therefore, NFAT3 influences the transcriptional activity of ERa through their interaction and potentially regulates ER-mediated signaling pathways. NFAT3 may play important roles in the development of breast cancer, and become a new target for therapy.