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

We studied the 24-hour plasma melatonin profile in three groups of women: normal individuals, women with breast cancer, and women at high risk for breast cancer, to determine the relationship of plasma melatonin to this malignancy. The mean daytime (nadir) and mean nighttime (peak) plasma levels for the normal subjects were 9.1 pg/mL and 70.9 pg/mL, respectively. The mean daytime and nighttime plasma levels, and the range of melatonin day to night differences for women with breast cancer and women at high risk for breast cancer were comparable to each other and to the normal subjects, with no statistically significant differences noted. The patients with breast cancer demonstrated a striking correlation between the melatonin diurnal rhythm and the steroid receptor content of the primary tumor. Women with estrogen (ER) or progesterone (PR) receptor-positive tumors had a significantly lower mean plasma melatonin day to night difference than did patients with ER- or PR-negative tumors. Further, a strong inverse correlation was observed between the plasma melatonin concentration and the quantities of ER and PR in the primary tumor: the lower the plasma melatonin concentration the greater the amount of either receptor in the primary tumor. Plasma melatonin did not correlate with tumor glucocorticoid receptor content or stage of breast cancer among these patients, or with menopausal status, age, parity, or the plasma levels of estrone, estradiol, progesterone, follicle-stimulating hormone (FSH), or luteinizing hormone (LH) among all individuals studied. Plasma melatonin was also independent of the degree of risk for breast cancer among the high-risk patients. These findings suggest an important relationship between the plasma melatonin diurnal rhythm and the hormone dependency of human breast cancer, and may have implications for both the prognosis and treatment of this malignancy.
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PMID:Plasma melatonin and the hormone-dependency of human breast cancer. 402 Apr 7

Ivalin is a plant alkaloid that inhibits the induction of tumors in animals. Phomopsin is a mycotoxin known to be carcinogenic. To determine if these compounds influence endocrine responsiveness, their effect on steroid receptors was measured. Neither of these toxins had a direct effect on either the binding capacity or the rate of steroid association of [3H]estradiol-17 beta, [3H]R5020, or [3H]dexamethasone to their respective receptors in cytosol of human breast cancer and rat liver. However, steroid receptor levels of MCF-7 cells, grown in tissue culture, were altered by ivalin and phomopsin. Ivalin at 10(-6) M depressed estrogen receptor levels, while glucocorticoid receptor levels were increased. At 10(-6) M, phomopsin was inhibitory of both progestin and glucocorticoid binding capacities. Data obtained from the proliferation of MCF-7 cells indicated that ivalin and phomopsin at 10(-6) M decreased the number of cells grown in tissue culture. Phomopsin exhibited an inhibitory effect on both [3H]thymidine and [3H]glycine incorporation, while ivalin stimulated [3H]glycine incorporation.
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PMID:Influence of phomopsin and ivalin on steroid-hormone binding and growth of MCF-7 human breast cancer cells. 406 51

Progestin, estrogen, androgen, glucocorticoid as well as mineralocorticoid receptors (PR, ER, AR, GR and MR, respectively) were all evaluated with specific synthetic radioligands (biochemical assays) in 25 meningiomas, 9 gliomas and 4 brain metastases. In meningiomas the main steroid hormone receptors appeared to be the progestin receptor, present in 24/25 cases (mean level: 7 105 fmol/gT) and the androgen receptor, present in 23/25 cases (mean level: 2 265 fmol/gT). Progestin receptor levels were found to be significantly lower in meningiomas of the fibroblastic subtype whereas none of the steroid hormone receptors were detected in the anaplastic case. On the other hand, glucocorticoid receptor levels were related to the preoperative glucocorticoid therapy. In gliomas only estrogen receptors (2/9 cases) and especially androgen receptors (8/9 cases) were noticeable: the latter seemed to be related to the histological types and to the sex of patients. No receptors were found in any of the four studied metastases, including one from breast cancer. The biochemical characterization of the receptors as well as their relevance to tumor biology and to the physiology of the normal tissues where tumors arise, were discussed, and biochemical data were compared with those previously reported.
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PMID:Steroid hormone receptors in human meningiomas, gliomas and brain metastases. 608 14

A study was made of basic mechanisms involved in regression of breast cancer exposed to high levels of synthetic progestins. The possibility that progestins act on breast cancer by way of the progesterone receptor mechanism and subsequent increase of estradiol 17 beta-dehydrogenase activity could not be confirmed in this investigation. It is demonstrated that the progestins megestrol acetate and medroxyprogesterone acetate are strong competitors for steroids which bind specifically to androgen, glucocorticoid, and progesterone receptors, indicating that the progestins are able to bind to these receptors with high affinity. In contrast, these progestins do not compete with estradiol for estrogen receptor binding. In 34 patients with progressive metastatic breast cancer, results of receptor studies have been correlated with clinical response during treatment with megestrol acetate. Statistically, regressions were significantly associated with tumors containing large amounts of androgen receptors. Clinical correlation with the quantities of glucocorticoid receptor was weak, while such correlations with estrogen and progesterone receptors were absent. However, we did demonstrate relationships between the quantities of the various receptors in breast cancer. Tumors containing a large amount of androgen receptors also generally contain estrogen receptors. It might be that a favorable response to progestins is confined to the group of patients with hormone-responsive breast cancers, as such characterized by the presence of estrogen receptors, and that within this group the actual androgen receptor levels determine response.
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PMID:Estrogen, androgen, glucocorticoid, and progesterone receptors in progestin-induced regression of human breast cancer. 624 8

The determination of estrogen and progesterone receptors in breast cancer has been shown to be useful in predicting the response to endocrine therapy. Given their well-known inhibitory effects on lymphoid tissue, glucocorticoids have been used widely in the treatment of leukemia. Given these facts, over the last 10 years, several investigators have measured the number of glucocorticoid receptors in normal and neoplastic lymphoid tissue to see whether their number correlated with glucocorticoid responsiveness in vitro or in vivo. No clear correlation could be established between the level of glucocorticoid receptor and the in vitro action of steroids in normal and neoplastic lymphoid tissue. In contrast, attempts to correlate glucocorticoid receptor levels in acute lymphocytic leukemia to in vivo steroid responsiveness and immunological type using the whole-cell-binding assay for receptor determination and selecting the patients according to age and immunological criteria have been more successful.
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PMID:Glucocorticoid receptors and steroid sensitivity in normal and neoplastic human lymphoid tissues: a review. 636 49

Measurement of estrogen receptor content in human breast cancer has become a valuable tool to predict the response of a tumor to endocrine manipulations. The aim of this study was to see whether steroid receptor assay could also be used to predict the value of endocrine therapy in human prostatic carcinoma. Biopsies from 25 primary tumors were analyzed with regard to quantity of methyltrienolone (a synthetic androgen) binding to the receptor 20 specimens were receptor-positive and 5 were receptor-negative. The correlation between receptor content and response to endocrine treatment was approximately approximately equal to 80%. The steroid receptor profiles of 5 lymph node metastases were also analyzed. 4/5 contained methyltrienolone receptors and 2/5 contained progestin receptors. 3/5 were glucocorticoid receptor-positive while all specimens were estrogen receptor-negative.
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PMID:Prediction of tumor response to endocrine therapy in prostatic carcinoma based on steroid receptor assay. 693 41

Progesterone receptor from rabbit uterine cytosol was purified to a specific activity of approximately 2 nmol of bound hormone per mg of protein. A goat was immunized with this preparation and, after two injections of 0.7-0.8 nmol, yielded antireceptor antibodies. The antiserum reacted with both cytosolic and nuclear rabbit progesterone receptor and also with progesterone receptor from other rabbit tissues (vagina and pituitary). A crossreaction was observed with progesterone receptors from other mammalian, especially human, tissues (cytosolic receptor from rat and guinea pig uterus, cytosolic receptor from human breast cancer, and nuclear receptor from human endometrium). On the contrary, there was no interaction with a nonmammalian receptor (chicken oviduct progesterone receptor). The antibodies did not crossreact with other rabbit steroid receptors (uterine estradiol receptor and liver glucocorticoid receptor) or with nonreceptor progesterone-binding proteins (transcortin from plasma and uteroglobin from uterine fluid).
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PMID:Antibodies to rabbit progesterone receptor: crossreaction with human receptor. 694 Jan 66

We have studied the effect of steroids on cell proliferation in two continuous cell lines derived from rat mammary tumors induced by 7, 12-dimethyl-benz (a) anthracene (DMBA) and N-nitrosomethylurea (NMU). These cell lines contain high concentrations of glucocorticoid and androgen receptors but no estrogen and progesterone receptors as previously shown (1). The cell proliferation was evaluated by measuring [3H] thymidine incorporation into DNA, cell number, and DNA content. Dexamethasone was found to markedly stimulate cell proliferation in a dose-dependent manner, suggesting that it was acting via the glucocorticoid receptor. The effect of 5 alpha-dihydrotestosterone (DHT) was weaker since a stimulation of [3H] thymidine incorporation was contrasted by the absence of a constant increase of cell proliferation. Progesterone partially stimulated NMU cell growth and totally inhibited the stimulatory effect of dexamethasone in both cell lines. The synthetic progestin R5020 displayed a similar activity to that of progesterone. These results show that progestins can directly modulate the growth of mammary cancer cells even in the absence of progesterone receptor by interacting on the glucocorticoid receptor. We conclude that progestins act mostly as partial agonist-antagonists of glucocorticoids in these two rat mammary adenocarcinoma cell lines.
Breast Cancer Res Treat 1981
PMID:Growth regulation of two rat adenocarcinoma cell lines by dexamethasone and progesterone. 734 82

The effects of long term treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) on estrogen receptor (ER) expression in the human breast cancer cell line, MCF-7, were studied. This study demonstrates that treatment of cells with the phorbol ester blocked estrogen receptor activity. Treatment of cells with 100 nM TPA resulted in an 80% decrease in the level of ER protein and a parallel decrease in ER mRNA and binding capacity. Following removal of TPA from the medium, the level of ER protein and mRNA returned to control values; however, the receptor failed to bind estradiol. These cells also failed to induce progesterone receptor in response to estradiol. In addition, TPA treatment blocked transcription from an estrogen response element in transient transfection assays and inhibited ER binding to its response element in a DNA mobility shift assay. The estrogen receptor in treated cells was recognized by two monoclonal anti-ER antibodies and was not quantitatively different from ER in control cells. RNase protection analysis failed to detect any qualitative changes in the ER mRNA transcript. Mixing experiments suggest that TPA induces/activates a factor which interacts with the ER to block binding of estradiol. The effects of TPA on ER levels and binding capacity were concentration-dependent. Low concentrations of TPA inhibited estradiol binding without a decrease in the level of protein, whereas higher concentrations were required to decrease the level of ER protein. The effects of TPA appear to be mediated by activation of protein kinase C since the protein kinase C inhibitors, H-7 and bryostatin, block the effects of TPA on estradiol induction of progesterone receptor. TPA treatment had no effect on the level or binding capacity of the glucocorticoid receptor, indicating that the effects are not universal for steroid receptors. These data demonstrate that activation of the protein kinase C signal transduction pathway modulates the estrogen receptor pathway. The long term effect of protein kinase C activation is to inhibit estrogen receptor function through induction/activation of a factor which interacts with the receptor.
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PMID:Effects of 12-O-tetradecanoylphorbol-13-acetate on estrogen receptor activity in MCF-7 cells. 755 63

The ability to respond to small signalling molecules such as steroid hormones is important for many physiological processes. Steroid hormones act through a group of high affinity receptors that regulate transcription by binding to hormone response elements (HREs) located within the promoters of target genes, which themselves are organized with nuclear proteins to form chromatin. To dissect the mechanisms(s) of steroid hormone action we have used the steroid inducible mouse mammary tumor virus (MMTV) promoter as a model system. The MMTV promoter is assembled into a phased array of nucleosomes that are specifically positioned in rodent cells. Induction of transcription by glucocorticoids is accompanied by the appearance of a hypersensitive region in the proximal promoter which allows the hormone dependent assembly of a preinitiation complex including transcription factors such as nuclear factor 1 (NF1) and the octamer transcription factor (OTF). Surprisingly, when introduced by transient transfection, the progesterone receptor (PR) is unable to activate this promoter in vivo, a finding that may result from its inability to alter MMTV promoter chromatin. In an attempt to investigate the failure of the PR to activate the promoter, we have stably introduced the MMTV promoter into human T47D breast cancer cells that express high levels of the PR. In contrast to what has been observed previously in rodent cells, the MMTV templates resident in human breast cancer cells adopt a novel and constitutively open chromatin structure. The constitutively open chromatin structure is accompanied by the hormone independent loading of transcription factors including the PR and NF1. In T47D cells that stably express the glucocorticoid receptor, the MMTV promoter responds to glucocorticoids, but not progestins, and displays glucocorticoid induced restriction enzyme hypersensitivity and transcription factor loading. These findings suggest that the organization of the MMTV chromatin structure is dependent upon the cell type and receptor status of the recipient cell into which the MMTV promoter is stably introduced.
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PMID:Steroid hormone receptor status defines the MMTV promoter chromatin structure in vivo. 762 91


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