Expression and significance of estrogen receptor isoforms in different breast tissues
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Objective To investigate the estrogen receptor(ER)isoforms ERα and ERβ expressions and their relationship with clinicopathological parameters in normal breast tissue,benign breast diseases,breast cancer in situ and invasive breast cancer tissue.Methods Breast tissue samples were obtained,including normal breast tissue(14 cases),benign breast diseases(35 cases),breast cancer in situ(8 cases)and invasive breast cancer(37 cases).Immunohistochemistry was used to measure the expressions of ERα and ERβ in the breast tissues.Results The profiles of the ERα and ERβ expressions in normal tissues and the tissues of benign breast diseases were similar.Compared with normal breast tissues and benign breast diseases,ERα protein level was down-regulated in the tissues of breast cancer in situ and invasive breast cancer significantly(P0.01);ERβ protein level was down-regulated in the tissues of invasive breast cancer notably(P0.01);The coexpression of ERα and ERβ was decreased in the tissues of breast cancer in situ and invasive breast cancer remarkably(P0.01).Conclusion ERβ may play a role in the human breast cancer probably by modulating ERα activity.Keywords:
Breast tissue
CA 15-3
Estrogen receptor beta
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Estrogen hormones have a large impact on both normal development and tumorigenesis of the breast.Breast tissue samples from 49 women undergoing surgery were included. The estrogen receptors (ERα and ERβ), ERα36 and G-coupled estrogen receptor-1 (GPER) were determined in benign and malignant breast tissue.The ERα36 and ERα mRNA levels were highest in malignant tumors. Stromal ERβ immunostaining in benign tumors was higher than in the paired normal tissue. GPER expression was lowest in benign tumors. In the malignant tumors, the Nottingham Prognostic Index (NPI) correlated positively with stromal GPER and the serum testosterone level. The serum insulin-like growth factor-1 (IGF-1) level correlated negatively with GPER mRNA and glandular ERα.The expression of ERα36 is stronger in malignant breast tissue. The strong positive correlation between NPI and GPER in malignant breast stroma indicates an important role for GPER in breast cancer prognosis.
GPER
Nottingham Prognostic Index
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Objective To detect quantitatively the expression of ERα and ERβ mRNA in primary breast cancer. Moreover to study the effect of ER subtype on breast cancer. Methods A quantitative analysis of ERα and ERβ mRNA expression in normal and breast cancer tissuesn=108 using real-time PCR assay. Results ERα mRNA levels in ERα-positive breast cancers were significantly(P 0.01) higher than those in ERα-negative breast cancers and normal breast tissues. ERβ mRNA levels in normal breast tissues were significantly (P0.01) higher than those in ERα-positive and ERα-negative breast cancers. Meanwhile ERβ mRNA levels in ERα-negative breast tissues were significantly (P 0.01) higher than those in ERα-positive breast cancers. ERβ mRNA levels did not show any significant correlation with age tumor size lymph node status and histological grade. Conclusion ERα mRNA is up-regulated and ERβ mRNA is down-regulated during carcinogenesis of breast cancers. It suggests that ERβ may perform an inhibit function in breast cancer.
Estrogen receptor alpha
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Breast tissue
Estrogen receptor beta
Estrogen receptor alpha
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e22094 Background: Oestrogen receptor positive (ER+) breast cancer (BC) is heterogeneous with regard to their clinical behaviour and response. The ER and Progesterone receptors (PgR) are currently the best predictors of response to the anti-oestrogen agent tamoxifen, yet up to 30–40% of ER+ breast cancers will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance is required. There has been an explosion of greater understanding since the arrival of new cutting-edge genomic profiling technology. Methods: RNA from the BC cell lines and frozen tissue was extracted and qualified using Qiagen Mini Kit and BioAgilent respectivelly. Probe preparation and scanning of the chips were carried out according to Affymetrix protocol. The normalisation and analysis of data (Limma) was performed using Bioconductor software. RT- PCR probes were purchased from Applied Biosystem and performed on ABI7500 instrument. The IHC-P was done using Ventana. TMA prepared with TMABooster, Alphelys (Plaisir, France). Results: Gene expression changes were studied in the TR breast cell lines MCF7 (tenovus), T47D and ZR by using the Affymetrix Hu133 plus 2.0 platform. Common genes of significant expression from the 3 TR cell lines were validated by real-time PCR (RT-PCR) and immuno-histochemistry (IHC-P) staining. 7 (MAGEA2, AKR1C3, VGLL1, THRAP5, GREB1, PDZK1, MYBL1, HnRNPA2B1, PGR) out of the 9 chosen genes were successfully validated. Proliferation studies on MageA2 overexpressing clones were performed. Stable overexpression of MageA2 in T47D and MCF-7 confers a proliferation advantage in tamoxifen-containing media as shown in proliferation and cell cycle analysis. MageA2 has been shown to alter the p53 pathway. The expression of KAP1, which interacts with p53 and inactivates it, was enhanced by MageA2 overexpression. In addition, overexpression of MageA2 is seen to increases histone deacetylase (HDAC3), and p53 expression as seen by immunoblotting. Validation of MageA2 on TMA of 100 patients is underway. Conclusions: MageA2 is a possible selective molecular target for the reversal of tamoxifen resistance. No significant financial relationships to disclose.
Progesterone receptor
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Objective:To investigate the regulating effect of estrogen on the expression of CD147 in human breast cancer cell line.Methods:ER positive MCF-7 human breast cancer cells were treated with estrogen for 24 hours.CD147 mRNA levels were examined by qRT-PCR before and after treatment.Western blot was used to examine CD147 protein levels.Results:In the ER positive human breast cancer cells,the expression of CD147 mRNA and protein increased after treated by estrogen.And there was no obvious effect in the ER negtive human breast cancer cells.Conclusion:Estrogen can activate the expression of CD147 though ER to promote growth and metastasis of breast cancer.
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The aim of the study was to investigate the effects of estrogen receptor (ER) subtypes (ERα and ERβ) on breast cancer development and progression. The expression level of ERα and ERβ in breast cancer tissues and paired normal breast tissues were detected by Western blot analysis and immunohistochemistry (IHC) staining. The features of ERα and ERβ status in cancer tissues or normal breast tissues and the correlations between clinicopathological characteristics and prognosis were analyzed. The expression levels of ERα and ERβ in breast cancer tissues are significantly lower than those in the paired normal tissues. The expression of ERβ is decreased more than that of ERα. ERα expression levels in cancer tissues are associated with tumor diameter, tumor–node–metastasis (TNM) stage, and progesterone receptor (PR) status. However, ERβ expression levels in cancer tissues are not correlated with clinicopathological factors of patients with breast cancer. In conclusion, ER subtypes might play different roles in the development of breast cancer.
Estrogen receptor beta
Progesterone receptor
Estrogen receptor alpha
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Objective:To detect the expression of estrogen receptor β(ERβ) protein in breast cancer, and to analyze the relationship between the expression of ERβ protein and the clinic pathologic behavior of breast cancer.Methods:The immunohistochemistry method was used to detect the expression of ERβ protein in 96 breast cancer samples.Results:The ERβ positiye rates in cancer and adjacent cancer tissues were 75.0%(72/96) and 90.5%(57/63) respectively. The difference was significant (P0. 05). The expression level of ERβ protein was associated with Erα protein level, PR protein level and tumor grade (P0.05), and there were no significant correlation with age, tumor size, axillary lymph node status, tumor pathological type, menopausal status. (P0.05).Conclusion:ERβ widely expresses in adjacent breast cancer tissues and also expresses in the cancer tissues, The expression in breast cancer tissues is lower than that in the adjacent cancer tissues. The positive expression of ERβ may be a valuable marker of favourable prognosis.
Estrogen receptor alpha
Progesterone receptor
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Objective To study the relationship of estrogen receptor-beta and its isoform expressions with tamoxifen resistance in human breast cancer. Methods Thirty patients of primary breast cancer whose disease progressed while on tamoxifen therapy (tamoxifen resistant) and 13 matched patients of primary breast cancer without disease progression (tamoxifen sensitive) were included. The expression of total estrogen receptor beta (ERβ), ERβ1 and ERβcx in the specimens were tested by IHC. Results High total ERβ protein expressions were more in tamoxifen sensitive tumors than resistant tumors (P0.05), while the expressions of ERβ1 and ERβcx protein showed no significant differences between the two groups. Conclusion The expressions of ERβ protein and its isoforms may differ in breast cancer patients who have different sensitivity to tamoxifen therapy.
Estrogen receptor beta
Progesterone receptor
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Steroid hormone receptors are used routinely to predict endocrine responsiveness in patients with breast cancer. Two oestrogen receptors (ERs): ER alpha and ER beta have been identified. Although ER alpha and ER beta genes share a large degree of homology, it is generally thought that their distribution and function are substantially different in many tissues. Both of them may be expressed in normal and neoplastic tissues of the breast. While much is known about ER alpha, the role of ER beta is still undefined, especially at the protein level. Recent development of reliable antibodies to ER beta has provided opportunity to test immunohistochemical reactions detecting ER beta in archival breast tumours. The aim of our study was to learn more about the cellular mechanisms underlying the relationship of ER beta and progesterone receptor (PR) in breast cancer tissues, discriminating between hormone-dependent and hormone-independent tumours. ER alpha and PR content of tumour tissues of 154 patients with breast cancer were tested by in situ indirect immunohistochemical method parallel with ligand binding biochemical assay. ER beta was detected in 8 ER alpha-/PR+ breast carcinomas by immunohistochemical method too. Steroid hormone receptor content was analysed comparing to the histologic type and grading of the tumours.A considerable part of breast carcinomas belongs to the ER+/PR+ and ER-/PR- groups. About 1-2% of the tumours is expected to be ER alpha-/ER beta+/PR+ type. In such cases ER alpha negative reaction together with PR positivity can signal the necessity of the immunohistochemical detection of ER beta in routine histopathological practice, presenting the precise steroid hormone receptor status for the most effective endocrine therapy of the patients.
Steroid hormone receptor
Progesterone receptor
Estrogen receptor alpha
Alpha (finance)
BETA (programming language)
Sex hormone receptor
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