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

Intermittent implantation of 600--1,300 microgram estriol subcutaneously beginning 48 h before oral administration of 7,12-dimethylbenz(a)anthracene or procarbazine prevents development of 80--90% of carcinomas of the breast occurring during the natural life span of the intact female Sprague-Dawley rat. Some estriol precursors were less inhibitory of breast cancer development among 23 other estrogens and androgens, progestins and glucocorticoids tested. More frequent or lower estriol doses than 100--200 microgram/kg/24 h every 2 months were less inhibitory of breast carcinogenesis. No other types of neoplasms were reduced in incidence by estriol implants, which also reduced uterine weights by 20--25%. Intermittent substitution of estriol for estrone or estradiol in the nuclear receptor complexes of target cells probably accounts for these observations, which resemble the effect of castration in reducing breast cancer incidence. Human studies indicate excellent tolerance for oral estriol doses of 10--200 microgram/kg/24 h, which may correct subnormal estriol/estrone + estradiol urinary quotients associated with elevated risk of breast carcinogenesis in epidemiologic investigations.
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PMID:Clinical and experimental aspects of the anti-mammary carinogenic activity of estriol. 9

The presence or absence of estrogen receptors in the nuclei of human breast tumor may be a useful tool in determining whether the tumor will or will not respond to endocrine therapy. This paper describes an assay which measures both unoccupied and occupied nuclear receptors in human breast cancer tumors. The assay was predicated on the fact that at low salt concentration, the nuclear receptor is bound to chromatin particles and can be separated from the soluble components containing proteolytic acitivity. Nuclear estradiol receptors were measured in human breast cancer tissue (MCF-7 cell line) and in DMBA (dimethylbenz(a)anthracene-induced rat mammary carcinomas) tumors. Complete translocation of the cytoplasmic receptor in the MCF-7 cells was observed compared to only 35-50% of the cytoplasmic receptors seen in the nucleus of the DMBA tumor after estradiol injection. The study also showed 6 pmol/mg DNA for total unoccupied nuclei and cytoplasmic estrogen receptors, and 25% of it in the nucleus; this finding differed from Zava et al's finding of 2 pmol/mg DNA and 75% in the nucleus, probably because of differing methodology or use of a later passage of cell line. 29 out of the 34 tumors with cytoplasmic receptors were found to contain unoccupied nuclear receptors, indicating that free nuclear receptors are not exceptions. The assay used in this study is currently being used to determine the translocative ability of the cytoplasmic receptors in human breast carcinomas.
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PMID:Estradiol binding to nuclear receptors in human breast cancer tissue (MCF-7 cell line) and in dimethylbenz(a)anthracene-induced mammary carcinoma. 10 64

Immunoglobulin obtained from the serum of rabbits immunized with a highly purified preparation of estradiol-receptor complex from calf uterine nuclei has been shown to contain specific antibodies to the receptor protein (estrophilin) by four criteria: (a) precipitation of the radioactive steroid upon addition of goat antibody against rabbit gamma globulin to a mixture of the tritiated estradiol-receptor complex and the immunoglobulin, (b) adsorption of the estradiol-receptor complex by the immunoglobulin linked to Sepharose, (c) adsorption of the estradiol-receptor complex in the presence of the immunoglobulin by Staphylococcus aureus protein-A linked to Sepharose, and (d) the ability of the immunoglobulin to increase the sedimentation rate of the estradiol-receptor complex. Antibodies to calf nuclear estrophilin were shown to crossreact with the nuclear receptor of rat uterus, as well as with the extranuclear receptor of calf, rat, mouse, and guinea pig uterus and of human breast cancer. The antibodies do not react with either the nuclear or extranuclear dihydrotestosterone-receptor complexes of rat prostate or with the extranuclear progesterone-receptor complex of chick oviduct. These findings indicate an immunochemical similarity among estrophilins from several mammalian species, as well as between extranuclear and nuclear forms of the receptor, but not among receptor proteins for different steroid hormones.
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PMID:Antibodies to estrogen receptor: immunochemical similarity of estrophilin from various mammalian species. 26 23

We have validated a hydroxylapatite assay for measuring estrogen receptor in extracts from breast tumor nuclei. By adsorption of receptor of hydroxylapatite prior to addition of radioactive ligand and warming, receptor degradation can be avoided. Total binding sites are measured at 30 degrees by exchange, and receptor sites unoccupied by steroid are measured at 4 degrees. A single saturating dose of 5 nM tritiated estradiol (with or without a 100-fold excess of nonradioactive diethylstilbestrol to estimate nonspecific binding) yields results similar to a six-dose Scatchard plot. Following in vivo injection of estradiol into rats bearing mammary tumors, receptor translocation in the tumors can be accurately quantitated with this assay. Applying the assay to human breast cancer, we find that tumor biopsies may contain cytoplasmic receptor alone or may also have appreciable nuclear receptor. The latter may be bound to estradiol or may be found in "free" form. The finding of free receptor in the nuclei in certain cases raises the possibility that unoccupied receptor might be able to stimulate cell replication in these cases, even in the absence of estrogen.
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PMID:An improved assay for nuclear estrogen receptor in experimental and human breast cancer. 88 77

The failure of the estrogen receptor test to predict unequivocally whether a breast cancer will respond to endocrine therapy has prompted us to re-examine the spectrum of responses that might be expected in a hormone-sensitive tissue. Three basic responses are recognized; initiation of DNA synthesis and cell proliferation; negative feedback; and autophagia. The expression of these responses may be partly or totally deficient in tumors. In some tumors, resistance to hormone may result from the lack of entry of hormone into the nucleus; in others the interaction of hormone with chromatin is probably abnormal Evidence is presented in support of the idea that the presence of steroid in the nucleus is strongly correlated to the presence of cytoplasmic receptor. The results also suggest that there is a strong link between the presence of steroid in the nucleus and the initiation of DNA synthesis. Finally the disappearance of nuclear receptor and the onset of autophagia seem to be related catabolic events.
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PMID:Steroid receptor proteins and regulation of growth in mammary tumors. 101 3

Nodal involvement is accepted as the best single marker of prognosis in breast cancer. However, there is little information on the sub-division of node-positive patients according to the oestrogen receptor status of the nodal tissue. We have previously reported (Eur. J. Ca. 1987, 23, 31) that, in almost all cases, involved nodes are only oestrogen receptor positive (ER+) in patients whose primary tumours are uniformly ER+. This paper presents clinical follow-up on a larger group of patients with node positive breast cancer. For each patient, both soluble and nuclear receptor concentrations were determined in three separate parts of the primary tumour and in at least one involved node (we have previously defined tumours which contained ER in all six fractions of the primary as HS++, those lacking receptor in some fractions as HS+- and wholly receptor negative tumours as HS--). Median follow-up time was 71.5 months. As expected, patients whose tumours were HS++ had a significant (P less than 0.008) survival advantage. More importantly, patients with ER in both the soluble and nuclear fractions of their involved nodes survived significantly (P less than 0.003) longer than those with ER- nodes. Thus, full oestrogen receptor status of involved nodes will give sufficient prognostic information when adequate primary tissue is not available.
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PMID:The prognosis of breast cancer patients in relation to the oestrogen receptor status of both primary disease and involved nodes. 163 67

We have studied by immunocytochemistry and monoclonal antibodies the presence and localization of estrogen receptors, progesterone receptors, and a 24-kD estrogen-regulated heat shock protein in biopsies from breast and endometrial cancer patients. Three different tissue processing protocols were used to colocalize the antigens in the same tissue sections: a) frozen sections, b) formalin fixation with routine paraffin embedding, and c) picric acid-formaldehyde (PAF) fixation with a rapid embedding in paraffin. Frozen sections showed good receptor staining but poor 24-kD protein immunoreactivity, while routine paraffin sections (with or without DNase pretreatment) were inadequate to reveal the nuclear receptor proteins at the same level seen in frozen sections. On the other hand, all three proteins could be detected satisfactorily in PAF-fixed paraffin-embedded tissue. Using this procedure we were able to visualize 24-kD protein and estrogen receptor or progesterone receptor in individual cells in paraffin sections. The study revealed that in all of the estrogen receptor positive breast and endometrial tumor samples, almost 90% of the cells expressing the cytoplasmic 24-kD protein contained estrogen receptor in the cell nucleus. In contrast, 24-kD immunoreactive cells did not express progesterone receptors in almost 40% of the progesterone receptor positive tumor samples.
Breast Cancer Res Treat 1990 Oct
PMID:Colocalization of estrogen and progesterone receptors with an estrogen-regulated heat shock protein in paraffin sections of human breast and endometrial cancer tissue. 208 75

Treatment of MCF-7 human breast cancer cells with 17 beta-[3H]estradiol resulted in a rapid accumulation of occupied nuclear estrogen receptor complex in which levels were maximized within 1 h and decreased after 3 h. Pretreatment of the cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 6 or 12 h prior to the addition of the radiolabeled hormone resulted in a 38 and 63% reduction in the levels of the occupied nuclear estrogen receptor, respectively, whereas addition of TCDD 1 h prior to the radioligand did not cause any significant change in the levels of the occupied nuclear receptor using velocity sedimentation analysis. Moreover, it was also shown with estrogen receptor antibodies that the TCDD-mediated dose-dependent decrease in occupied nuclear receptor levels was paralleled by a comparable decrease in immunoreactive protein at concentrations of 10(-8) to 10(-11) M TCDD. The reduction in levels of the occupied nuclear estrogen receptor was not due to increased estradiol metabolism since a significant reduction was observed at TCDD concentrations (10(-11) to 10(-13) M) which do not induce cytochrome P-450-dependent monooxygenase enzyme activities in MCF-7 cells. Treatment of the MCF-7 cells with actinomycin D or cycloheximide resulted in a greater than 2-fold increase in levels of the occupied nuclear estrogen receptor, and cotreatment of the cells with both TCDD and these inhibitors significantly decreased levels of the nuclear estrogen receptor complex. The structure-activity relationships for TCDD and several congeners were similar for both the reduction of occupied nuclear estrogen receptor levels and several aryl hydrocarbon (Ah) receptor agonist activities, and these results support a role of the Ah receptor in these processes.
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PMID:Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds on the occupied nuclear estrogen receptor in MCF-7 human breast cancer cells. 234 May 6

"Receptogram Analysis" has been developed as a pattern-oriented approach for predicting endocrine response in breast cancer based upon quantification of the estrogen receptor immunocytochemical assay (ERICA), using a Quantimet Imaging System. Response prediction was evaluated in 58 stage III and IV patients receiving endocrine therapy (primarily Tamoxifen). The Receptogram is a composite of the univariate distributions of nuclear receptor content, IOD(S), and concentration (MOD), and their bivariate contour plot; where (S) is the calculated nuclear radius in section. MOD distributions were classified into four types based upon peak modality and kurtosis (I-IV), and contour plots were classified into four subtypes (A-D) based upon contour slope. Patients failing therapy were ERICA--or their receptogram revealed co-existent ER+ and ER- tumor cells (type II), highly skewed MOD distributions lacking defined peaks (type IV), or contours with nearly horizontal slope (type C). Response was realized in 9/16 type I patients, with a single positive MOD peak, and in 9/15 type III patients, with discrete, multimodal MOD peaks. In contrast, 0/8 type II, 0/12 type IV, and 0/10 type C patients were responders. Receptogram analysis was superior to cytosol assay (DCC) as a response discriminant: positive predictive value, 53% vs. 33%; negative predictive value, 100% vs. 75%; sensitivity, 100% vs. 83%; specificity, 68% vs. 23%; and accuracy, 78% vs. 41%, respectively. Alternately, patients were assigned to potentially responsive or non-responsive groups based upon thresholded mean receptor parameters: field MOD, mean nuclear MOD (NMOD), and mean NMOD(PF) where PF is the ER+ nuclear fraction. While these parameters correlated with DCC (r = .72, 0.69, and 0.69), they were only marginally better in predictive value.
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PMID:Quantitative imaging of immunocytochemical (PAP) estrogen receptor staining patterns in breast cancer sections. 234 Jul 73

Using crude progesterone receptor preparations from T47D human breast cancer cells, we show by immunoprecipitation assay that receptor specifically and with high affinity recognizes the hormone response element (HRE) of the mouse mammary tumor virus (MMTV). The use of crude preparations minimizes alterations of receptors or loss of associated factors that may occur during purification. Specific binding was obtained at 1:1 molar ratios of receptor to DNA, and HRE sequences are recognized with an affinity at least 3 orders of magnitude greater than nonspecific DNA. We have compared the DNA-binding activities of different forms of progesterone receptors. The unliganded 8S cytosol receptor had low but detectable binding activity for MMTV DNA. Addition of hormone to cytosol produced a small but consistent 2.5-fold increase. In vitro methods of transforming cytosol receptors from an 8S to a 4S species failed to increase DNA-binding further. By contrast, 4S receptors bound by R5020 in whole cells and extracted from nuclei by salt, displayed a substantially higher (average, 11-fold) binding activity than an equal number of unliganded cytosol receptors. The dissociation constants for cytosol and nuclear receptor binding to MMTV DNA were similar (approximately 2 x 10(-9) M). Thus, nuclear receptors possess a higher capacity for binding to specific recognition sequences. These results suggest that hormone or a hormone-dependent mechanism increases the intrinsic DNA-binding activity of receptors independent of receptor transformation from 8S to 4S. Further experiments indicate that a nonreceptor activity in nuclear extracts can increase the sequence-specific DNA-binding activity of cytosol receptors. This activity is present in both T47D cells and receptor-negative MDA-231 cells. We conclude that the higher DNA-binding activity of the nuclear receptor-hormone complex is due in part to receptor interaction with other nuclear proteins or factors. Such interactions may function to maintain receptors in a disaggregated active complex or to stabilize their binding to specific DNA sites.
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PMID:Human progesterone receptor binding to mouse mammary tumor virus deoxyribonucleic acid: dependence on hormone and nonreceptor nuclear factor(s). 254 Apr 30


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