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

Although cloning of ER beta has prompted a reevaluation of the role of ERs in human breast cancer and there have been many studies focusing on the clinical value of ER beta detection, however, few reports evaluated the prognostic significance of ER beta based on follow-up data. The VEGF gene transcription may be mediated by different ER subtypes directly. The aim of this study was to evaluate the relationship of angiogenesis factor VEGF with different ER subtypes and the prognostic value of ER beta and VEGF in 116 human breast cancer patients. Of these patients, 40 (34.5%) were ER beta protein high expressed and 76 (65.5%) were ER beta protein low expressed. When correlated the ER beta protein levels with other clinical characteristics, statistical significance (p<0.05) was found between ER beta protein expression and menopausal status, and tumor grade. No significance was found between ER beta protein level and node status, stage, or tumor size. Inverse relationship was found between ER beta protein expression and PR status (p<0.05). When comparing the VEGF levels with different ER subtypes a significant difference between ERs and VEGF was found. In ER beta protein high expression group, the VEGF protein was highly expressed (p<0.01), inverse relationship was also found between ER alpha and VEGF. In univariate analysis ER alpha, ER beta and VEGF levels had prognostic value for both relapse-free survival and overall survival (p<0.05). However, in a multivariate study, ER beta and ER alpha protein levels lost the prognostic value either to relapse-free survival or to overall survival. Only VEGF levels acted as an independent prognostic factor to disease-free survival. The result suggested that ER beta protein may have important prognostic value in human breast cancer patients. VEGF expression may be mediated through different ER subtypes.
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PMID:The expression of ER beta protein correlates with vascular endothelial growth factor and its prognostic significance in human breast cancer. 1216 51

Estrogens control a variety of physiological and disease-linked processes, most notably reproduction, bone remodeling and breast cancer, and their effects are transduced through classic unclear receptors referred to as estrogen receptor-alpha (ER alpha) and ER beta. Recent results obtained using the estrogen-related receptors (ERR alpha, -beta and -gamma), a subfamily of orphan nuclear receptors closely related to the ERs, have shown that the ERRs share target genes, coregulatory proteins, ligands and sites of action with the ERs. In addition, the ERRs can actively influence the estrogenic response, suggesting that pharmacological modulation of ERR activity will be clinically useful to prevent and/or treat a variety of conditions related to women's health.
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PMID:To ERR in the estrogen pathway. 1218 69

The effect of adjuvant tamoxifen treatment on bone mineral density (BMD) and bone turnover markers was studied in postmenopausal breast cancer patients. The relationship of tamoxifen's effect with the genetic polymorphisms of estrogen receptor (ER)-alpha and ER-beta gene was also studied. Twenty-one postmenopausal breast cancer patients were given tamoxifen (20 mg/day) as the adjuvant treatment after the surgery. BMD of the lumbar supine (dual emission X-rays absorptiometry) and bone resorption (deoxypyridinoline, aminoterminal telopeptide of type I collagen, and carboxyterminal telopeptide of type I collagen) and formation (propeptide of type I procollagen, osteocalcin, and bone-specific alkaline phosphatase) markers were examined at baseline (before the surgery), 6 and 12 months after the start of tamoxifen treatment. Genetic polymorphisms analyzed were TA dinucleotide repeats polymorphism in the promoter region and PvuII and XbaI restriction fragment length polymorphism for the ER-alpha gene and the CA dinucleotide repeats polymorphism in the intron 5 for the ER-beta gene. Tamoxifen significantly increased BMD of the lumbar spine at both 6 (P<0.01) and 12 months (P<0.01) after the start of tamoxifen as compared with that at baseline. The mean percent increase in BMD was 3.3% at 6 months and 2.7% at 12 months. All bone resorption and formation markers significantly decreased at both 6 and 12 months. Among the four genetic polymorphisms studied, only ER-beta CA repeat polymorphism was found to be significantly associated with BMD at 12 months, i.e. BMD of the 21 CA repeats allele carriers was significantly higher than that of the non-carriers (P=0.025). These results suggest that tamoxifen increases BMD of the lumbar supine by reducing the bone turnover in postmenopausal breast cancer patients, and this bone restoring effect of tamoxifen is more marked in ER-beta 21 CA repeats allele carriers than non-carriers.
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PMID:Influence of adjuvant tamoxifen treatment on bone mineral density and bone turnover markers in postmenopausal breast cancer patients in Japan. 1221 92

Raloxifene, a selective estrogen receptor (ER) modulator, is a mixed estrogen agonist/antagonist that has been shown to prevent osteoporosis and breast cancer in women. Because the prostate contains high levels of ER-beta, the present study investigated the effect of raloxifene in three well-characterized, androgen-independent human prostate cancer cell lines: (a) PC3; (b) PC3M; and (c) DU145. Reverse transcriptase-PCR and Western blot analysis for ER-alpha and ER-beta demonstrated that all three cell lines express ER-beta, whereas only PC3 and PC3M cells were positive for ER-alpha. After the treatment with raloxifene, a dramatic increase in cell death was observed in a dose-dependent manner in the three prostate cancer cell lines (10(-9) to 10(-6) M range). Because the three prostate cancer cell lines demonstrated similar morphological changes after the raloxifene treatment, PC3 (ER-alpha/ER-beta+) and DU145 (ER-beta+ only) cells were selected to further characterize the raloxifene-induced cell death. Using the nucleus-specific stain 4',6-diamidino-2-phenylindole, nuclear fragmentation was observed in a time-dependent manner in both cell lines after exposure to 10(-6) M raloxifene. Using the terminal deoxynucleotidyl transferase-mediated nick end labeling apoptotic assay, it was demonstrated that the nuclear fragmentation was caused by apoptosis. To investigate the possibility that caspase activation is involved in raloxifene-induced apoptosis, cells were treated with the pan-caspase inhibitor ZVAD. The results demonstrated that the dramatic change in cellular morphology after treatment with raloxifene was no longer observed when cells were pretreated with ZVAD. Immunoblot demonstrated activation of caspases 8 and 9 in PC3 and DU145 cells, respectively. Taken together, these results demonstrate that the mixed estrogen agonist/antagonist, raloxifene, induces apoptosis in androgen-independent human prostate cancer cell lines.
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PMID:Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis in androgen-independent human prostate cancer cell lines. 1223 8

Although numerous reports exist on the potential beneficial role of nutritional phytoestrogens in human health, their molecular mechanism in target cells is still not completely understood. Phytoestrogens promote estrogen and antiestrogen effects by interacting with numerous molecules, carrier proteins, enzymes and membrane and nuclear receptors, directly or indirectly involved in the transfer of estrogen signals. The hypothesis that the ER beta subtype plays a key role in antiproliferative effect of phytoestrogens, especially in breast cancer, is examined here. This review focus on the effects of phytoestrogens in developmental processes such as those linked to reproductive function, tumorigenesis and angiogenesis.
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PMID:Phytoestrogens as modulators of steroid action in target cells. 1227 Feb 16

Since 1996 when estrogen receptor beta(ER beta) was discovered, much effort has been devoted to the question of the value of ER beta as a prognostic and/or predictive factor in breast cancer and its potential as a novel target for pharmacological intervention. When estrogen receptors are applied on sucrose gradients and quantified by ligand binding, we found that in contrast to ER alpha, which has a narrow tissue distribution, ER beta is expressed in many tissues including both normal and malignant breast tissue. Receptor protein levels in tissues can also be measured from the intensities of bands after Western blotting and can be quantified when purified and quantified receptor is used as a standard. With this technique, we found that there were some tumors which had over 600 fmol/mg of ER beta protein but no detectable estradiol binding. In such tumors, RT-PCR analysis revealed that ER beta cx is the only ER beta isoform present. ER beta cx is a splice variant which utilizes an alternative exon 8. This change in the C-terminus results in very poor binding to estradiol (E2) and has a dominant negative effect on ER alpha function. Immunohistochemical analysis with an ER beta cx specific antibody in 115 ER alpha-positive breast cancers revealed that about half of the samples expressed ER beta cx protein. Initial analysis of samples from patients with preoperative tamoxifen treatment revealed that ER alpha-positive tumors expressing ER beta cx and lacking PR seemed to be resistant to the anti-estrogen. We conclude that, in order to better characterize breast cancers and design appropriate therapy for individual patients, assays for ER beta cx must be made available to clinicians.
Breast Cancer 2002
PMID:Clinical impact of assay of estrogen receptor beta cx in breast cancer. 1245 10

In recent years, several lines of epidemiologic, clinical and experimental evidences have been reported showing that estrogen hormones may be involved in malignant colorectal tumors. The sex differences in site-specific incidence, the increased incidence of colonic cancer in women with breast cancer, the protective effect of increasing parity and the reduced risk among women taking postmenopausal hormones, are all elements suggesting that sex hormones may play a role. Male rats experimentally exposed to the carcinogen dimethylhydrazine, have twice the risk of developing colon cancer and significantly shorter survival times than their female counterparts. Along with the clinical, experimental and epidemiologic findings there are also biologic reasons why estrogen may be protective. Most estrogen action appears to be exerted via the estrogen receptors (ERs) on target cells. ERs have been reported in several solid tumors including gastrointestinal neoplasms such as esophageal, gallbladder, gastric and colorectal cancer. At the end of 1995, a second ER (ER-beta) was cloned from the rat prostate cDNA library and subsequently, the human and mouse homologs. Its demonstration in normal and neoplastic human colorectal tissues and "in vitro" in colonic epithelial cells, has renewed interest in investigating the existence of two ER subtypes. The presence of two ERs could explain the selective actions of estrogens on different target tissues and, particularly, on the gastrointestinal tract. Finally, our studies suggest that estrogens and their receptors play an important role in the growth and progression of colorectal tumors, by interacting with other molecules required for cell proliferation like growth factors and polyamines.
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PMID:Estrogens and colorectal cancer. 1247 78

Estrogens occurring naturally in the body are metabolized to catecholestrogens (2- and 4-hydroxyestradiol) by the cytochrome P450 enzymes. 2-Hydroxy catecholestrogens are further metabolized by catechol-O-methyltransferase to 2-methoxyestradiol, which is known to be protective against tumor formation. 2-Methoxyestradiol exhibits potent apoptotic activity against rapidly growing tumor cells. It also possesses antiangiogenic activity through a direct apoptotic effect on endothelial cells. Other molecular mechanisms, including microtubule stabilization by inhibition of the colchicine-binding site, have been reported. The exact mechanism of action of 2-methoxyestradiol is still unclear, but it has been shown to be effective in preventing tumor growth in a variety of cell lines. 2-Methoxyestradiol also possesses cardioprotective activity by inhibiting vascular smooth muscle cell growth in arteries. It has a lower binding affinity for estrogen receptor alpha compared with that of estradiol, and its affinity for estrogen receptor beta is even lower than that of estrogen receptor alpha, thus it has minimal estrogenic activity. 2-Methoxyestradiol is distinct because of its inability to engage estrogen receptors as an agonist, and its unique antiproliferative and apoptotic activities are mediated independently of estrogen receptors alpha and beta. A phase I clinical trial of 2-methoxyestradiol 200, 400, 600, 800, and 1,000 mg/day in 15 patients with breast cancer showed significant reduction in bone pain and analgesic intake in some patients, with no significant adverse effects. Another phase I study of 2-methoxyestradiol 200-1,000 mg/day in combination with docetaxel 35 mg/m2/week for 4-6 weeks performed in 15 patients with advanced refractory metastatic breast cancer showed no serious drug-related adverse effects. A phase II randomized, double-blind trial of 2-methoxyestradiol 400 and 1,200 mg/day in 33 patients with hormone-refractory prostate cancer showed that it was well tolerated and showed prostate specific antigen stabilizations and declines. We have started a phase I clinical trial to explore dosages greater than 1,000 mg/day.
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PMID:2-Methoxyestradiol, a promising anticancer agent. 1258 5

Licorice root contains chemically diverse compounds that exhibit estrogenic effects in vitro and in vivo. The chalcone isoliquiritigenin (ISL) is a component of licorice extract exhibiting either antitumorigenic activity or estrogen receptor (ER) alpha-dependent growth promoting effects on breast cancer cells. In order to contribute to a better understanding of this apparent paradox, we synthesized and ascertained the estrogenic properties of ISL using, as model systems, the hormone-sensitive MCF7 breast cancer cells and the steroid-independent HeLa cells. Transfection experiments reveal that ISL is able to transactivate the endogenous ER alpha in MCF7 cells and this is supported by the capability to induce down-regulation of ER alpha protein levels and up-regulation of pS2 mRNA. Moreover, by using chimeric proteins consisting of the hormone binding domains of ER alpha and ER beta fused to the Gal4 DNA binding domain, we have determined that ISL is an estrogenic agonist of both ER isoforms. As a biological counterpart, low and intermediate ISL concentrations that induce substantial transcriptional activity stimulate the proliferation of MCF7 cells. However, high levels of ISL become cytotoxic even in steroid-receptor negative HeLa cells. Thus, the activity of ISL and the balance between risk or chemopreventive factor for estrogen-dependent breast cancer may depend on dietary intake.
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PMID:Estrogenic and antiproliferative activities of isoliquiritigenin in MCF7 breast cancer cells. 1258 38

Aromatase, the product of the CYP19 gene, plays a key role in androgenic steroids transformation into estrogens from various hormonal sensitive tissues. Thus, in situ expression of CYP19 has been suggested to be involved in breast tumor growth especially in post-menopausal patients.We developed a real-time quantitative RT-PCR assay based on fluorescent TaqMan methodology to quantify total CYP19 gene expression at the mRNA level in breast tumors. This method, based on nucleic acid quantification in homogeneous solutions, has the potential to become a standard in terms of its sensitivity, wide dynamic range and high-throughput capacity. In a well-defined series of 107 post-menopausal breast tumor samples, relative CYP19 mRNA levels ranged from 1 to 131. Among the four major CYP19 exon I-spliced transcripts, designated I.a, I.b, I.c and I.d, mRNA levels of the latter three correlated positively with total CYP19 mRNA levels. In ER alpha-positive breast tumors, CYP19 and ER alpha mRNA levels correlated negatively with each other (P=0.0078, r=-0.266), while CYP19 and ER beta mRNA levels correlated positively (P=0.00012, r=+0.388). Patients with high CYP19 mRNA levels did not relapse more frequently or have shorter relapse-free survival than other patients. Finally, mRNA levels of IL6, a major CYP19 regulatory factor, were significantly higher in tumors strongly expressing CYP19 than in tumors weakly expressing CYP19 (P=0.018). In conclusion, CYP19 expression did not influence the outcome of post-menopausal patients with breast cancer.
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PMID:Real-time reverse transcription PCR assay of CYP19 expression: application to a well-defined series of post-menopausal breast carcinomas. 1258 39


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