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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nuclear receptor coactivator amplified in breast cancer 1 (AIB1) and its more active isoform AIB1-Delta3 are overexpressed in breast cancer and preneoplastic breast tissue. However, the impact of these proteins on the transcriptional activity of natural estrogens or selective estrogen receptor modulators (SERMs) has not been determined. Here we show that AIB1-Delta3 causes a significant increase in the efficacy of 17beta-estradiol at both estrogen receptor-alpha (ER-alpha) and ER-beta in ovarian, breast and endometrial cancer cell lines. AIB1-Delta3 also significantly increased the efficacy of the natural estrogen genistein at both ER-alpha and ER-beta, whereas AIB1 had no effect on either the potency or efficacy of genistein at either receptor. The estrogenic efficacy of the partial agonist tamoxifen was significantly increased in all cell lines at ER-alpha by overexpression of AIB1-Delta3 both on transfected and endogenous estrogen responsive genes. In contrast, overexpression of AIB1 or AIB1-Delta3 had no effect on the potency or efficacy of the SERM raloxifene. We conclude that overexpression of the AIB1-Delta3 isoform will increase the estrogenicity of a variety of natural and pharmacologic compounds in tissues that develop hormone-dependent neoplasias and overexpression of these cofactors may be a contributing factor to the hormone-driven development of neoplasia and to antiestrogen resistance of breast cancers.
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PMID:Impact of the nuclear receptor coactivator AIB1 isoform AIB1-Delta3 on estrogenic ligands with different intrinsic activity. 1469 61

An important new concept associated with estrogen receptor (ER) function in breast cancer is that ER status/ phenotype is multifaceted. In particular, the two full-length, ligand binding ERs (ER-alpha and ER-beta) and possibly multiple variant isoforms of ER must be considered. In addition, cross-talk factors that can influence ER activity in a ligand independent fashion and factors downstream of the ER, including coactivators and corepressors, clearly have important roles in ER function. Their careful evaluation in addition to ER status will be necessary to more fully understand the etiology of breast cancer and the changes occurring in estrogen signaling during breast tumorigenesis and breast cancer progression. Such knowledge is necessary to have a significant impact on better prevention and treatment strategies for human breast cancer.
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PMID:New insights into estrogen receptor function in human breast cancer. 1470 71

Estrogen receptor (ER)-alpha and ER-beta function as transcription factors, and both interact with nuclear regulatory proteins to enhance or inhibit transcription. We hypothesized that coregulators are expressed in breast cancer and may be differentially recruited by ERs in the presence of estrogen and tamoxifen. ER-beta was found to be expressed more frequently in node-negative patients (P < 0.05). Expression of steroid receptor coactivator-1 (SRC-1) was associated with nodal positivity (P < 0.05) and resistance to endocrine treatment (P < 0.001). The spatial coexpression of ER-alpha, ER-beta, and the coregulatory proteins was established using immunofluorescence. In both cell lines (MCF-7 and T47D) and in primary breast cancer cell cultures, beta-estradiol up-regulated ER-beta and coregulator protein expression and increased ER-alpha/ER-beta interaction with the estrogen response element (ERE). 4- Hydroxy-tamoxifen (4-OHT) increased ER-alpha and silencing mediator for retinoid and thyroid receptors (SMRT) expression and increased ER-ERE binding. SRC-1 and SMRT were identified at the ER-ERE complex, and interactions between ER isoforms and coregulatory proteins were determined using immunoprecipitation. Both ER-alpha and ER-beta preferentially bound SRC-1 in the presence of beta-estradiol. Conversely, in cells treated with 4-OHT, ER-alpha and ER-beta bound SMRT. Differential recruitment of SRC-1 and SMRT by ER-alpha and ER-beta in the presence of beta-estradiol and 4-OHT may be central to the response of the tumor to endocrine treatment.
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PMID:Differential recruitment of coregulator proteins steroid receptor coactivator-1 and silencing mediator for retinoid and thyroid receptors to the estrogen receptor-estrogen response element by beta-estradiol and 4-hydroxytamoxifen in human breast cancer. 1471 75

One of the main prognostic markers measured in breast tumours is oestrogen receptor (ER) status. With the discovery of ER beta, it has been necessary to re-evaluate ER signalling and the role of ER in breast cancer. Preliminary reports on ER beta signalling suggest it might induce opposite effects to those of ER alpha. To further understand the biology of breast cancer, the role each ER plays in disease progression must be established. This review summarizes the current understanding of ER beta and discusses some of the published work on the role of ER alpha and ER beta in breast cancer.
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PMID:The oestrogen receptors (ER alpha and ER beta) and their role in breast cancer: a review. 1473 94

Estrogens are important for the development and function of the normal mammary gland as well as for development of mammary cancer. The frontline therapy for treatment of estrogen receptor (ER alpha) positive breast cancer is antiestrogens. A second estrogen receptor (ER beta) is also expressed in the breast but it has not been measured because it is not detected by the immunoassays used to detect ER alpha. In many cell systems ER beta has actions which are opposite to those of ER alpha and this finding has raised questions about the role of ER beta in the development and treatment of breast cancer.
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PMID:The normal and malignant mammary gland: a fresh look with ER beta onboard. 1497 91

Oestrogen receptor (ER) alpha is a well established prognostic marker in breast cancer, and all patients who are ER alpha positive receive tamoxifen as adjuvant endocrine therapy. Although ER alpha predicts a favourable disease outcome, the usefulness of ER beta as a clinical prognostic marker remains to be defined. Here, we outline the history of both ERs and discuss the implications ER beta has to patients with breast cancer.
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PMID:Oestrogen receptor beta: what it means for patients with breast cancer. 1500 1

Estrogens work along with genetic changes to promote the development and growth of breast cancers. Because estrogenic hormones act via the estrogen receptors (ERs), ER-alpha and ER-beta, and the ER is present in more than half of breast tumors, this receptor has been the most widely targeted protein in breast cancer therapy. The presence of the ER in breast tumors predicts improved disease-free survival and response to selective ER modulators (SERMs), such as tamoxifen, or other forms of endocrine therapy. Suppression of ER activity by SERMs has proven to be a great benefit in the treatment of breast cancers and also in the prevention of breast cancer in women at high risk for the disease. The Study of Tamoxifen and Raloxifene trial comparing tamoxifen versus raloxifene effectiveness in breast cancer prevention is currently under way. To understand the balance of beneficial and undesirable effects of SERMs and to optimize their effectiveness, current investigations seek to characterize the genes activated or suppressed by these agents. Elucidation of the gene networks and cell signaling pathways under estrogen and SERM regulation and a clearer definition of the respective roles of ER-alpha and ER-beta and their coregulators in the actions of selective ER ligands, should enable the identification of new gene targets for therapeutic intervention and the development of novel drugs for the optimal treatment and prevention of breast cancer.
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PMID:Therapeutic targeting in the estrogen receptor hormonal pathway. 1505 41

Lung cancer is the leading cause of cancer death in US women and is responsible for as many deaths as breast cancer and all gynecological cancers combined. Most lung cancer is caused by cigarette smoke. Despite all that is known about the devastating effects of cigarettes, one quarter of women in the United States continue to smoke. Women are targeted in tobacco advertising, and teenage girls are often drawn to cigarette smoking under a variety of social pressures. Following the increase in smoking, the death rate from lung cancer in US women rose 600% from 1930 to 1997. Women may be more susceptible than men to the carcinogenic properties of cigarette smoke. In addition, differences in the biology of lung cancer exist between the 2 sexes with higher levels of DNA adduct formation, increased CYP1A1 expression, decreased DNA repair capacity, and increased incidence of K-ras gene mutations in women. The novel estrogen receptor beta has also been detected in lung tumors and suggests that estrogen signaling may have a biological role in tumorigenesis. Given these differences and given the enormous toll this disease has on US women, undertaking sex-specific research in lung cancer is crucial. Finally, disseminating information about this epidemic may prevent a similar epidemic in other parts of the world where women are just now becoming addicted to tobacco.
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PMID:Lung cancer in US women: a contemporary epidemic. 1508 4

This article describes the development and validation of two fluorescent receptor assays for the hRec-estrogen receptor subtypes alpha and beta. As a labelled ligand an autofluorescent phyto-estrogen (coumestrol) has been used. The estrogen receptor (ER) belongs to the nuclear receptor family, a class of soluble DNA binding proteins, mainly present in the cytoplasm of the cell, that act as ligand-activated enhancer factors. It consists of two different forms, expressed as ER-alpha (66 kDa) and ER-beta (59 kDa). The ER-alpha is mainly located in the uterus and the ER-beta can be found in vascular tissue. Detection and identification of compounds having estrogenic effects is of importance in drug discovery programmes within the pharmaceutical industry for their search for ER-subtype selective (ant)agonists which may prove to be of therapeutic value in treating a variety of estrogen-linked pathologies (breast cancer, osteoporosis, cardiovascular disease, type II diabetes and Alzheimer disease). Furthermore, interactions of (xeno-)estrogens with the endogenous hormonal system of the exposed organism can affect embryos, gonads, and reproductive behaviour. The latter can eventually lead to reduced reproduction and deterioration of a population. For that reason, monitoring of (xeno-)estrogens in food products and in the environment, attracts considerable attention by health councils throughout the world. The following characteristics were obtained for the human recombinant (hRec) estrogen receptor-beta assay, which is suitable for ER subtype selective drug-discovery purposes (IC50 values for 17-beta-estradiol and genistein were 5.1 nM and 25 nM, respectively): goodness of fit (R2) was always > 0.98 (x = 0.9933, n = 10). LLOQ of the assay is typically > or = 500 picomolar, whereas the ULOQ of the assay is < or = 20.0 nanomolar. For the hRec-estrogen receptor-alpha assay, which is suitable for monitoring of (xeno-)estrogens (IC50 values for 17-beta-estradiol and genistein were 0.68 nM and 65 nM, respectively) the following characteristics were obtained: goodness of fit (R2) was always > 0.96 (x = 0.9838, n = 10). LLOQ of the assay is typically > or = 200 picomolar, whereas the ULOQ of the assay is < or = 5.0 nanomolar.
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PMID:Development and validation of fluorescent receptor assays based on the human recombinant estrogen receptor subtypes alpha and beta. 1512 23

We have studied the effect of the aryl hydrocarbon receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on estrogen receptor (ER) beta gene expression in the human breast cancer cell line, T47D. TCDD inhibited 17beta-estradiol (E2)-induced up-regulation of both ER beta wild type and ER beta cx mRNA. Cycloheximide pre-treatment had no inhibitory effect, and the estimated half-life of ER beta mRNA of about 33 min was not changed by any hormone administration. Chromatin immunoprecipitation experiments showed recruitment of ER alpha to the ER beta promoter. Gel mobility shift experiments revealed an E2-induced protein binding to a half site estrogen response element in the ER beta promoter, and TCDD reduced that binding. These results show that ER alpha regulates the expression of its own heterodimerization partner, ER beta, in T47D cells. TCDD, an anti-estrogenic compound, inhibits ER alpha-mediated induction of ER beta mRNA. These findings add to our understanding of cross talk between dioxin and estrogen signaling in human cells.
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PMID:The Ah receptor inhibits estrogen-induced estrogen receptor beta in breast cancer cells. 1520 4


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