Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

Longitudinal studies on human growth have revealed seasonal patterns in the gain of height in 1/3 of the population. Seasonal sensitivity of growth velocity is apparently linked with a lean body structure. This being so, a subgroup with specific biological features could be isolated, including specific endocrine mechanisms (e.g. shorter interval between menarche and menopause, higher incidence of irregular early postmenstrual cycles, and higher concentration of growth hormone secretion) and specific metabolic pathways (more frequent drinking, smoking, and use of the contraceptive pill). This biological specificity may be responsible for behavioral heterogeneity in cancer in general and in breast malignancies in particular. One third of the breast cancer patient population is hormone responsive. The response to all the methods of cancer adjuvant therapy (including ablation of hormone producing organs, chemotherapy, and immunologic manipulation) used up till now does not surpass 33% in the long run. Breast cancer risk reduction by 1/3 due to full-term teenage pregnancies suggests that this may be a consequence of the interruption of a premalignant process initiated in women of the aforementioned subgroup. Simulation of early pregnancy might therefore lead to prevention of breast cancer in women who had seasonal growth patterns as children.
Breast Cancer Res Treat 1990 May
PMID:Host heterogeneity in female breast cancer: possible significance for pathophysiology, therapy, and prevention. 237 72

In this pilot clinical trial conducted in 10 postmenopausal women with advanced breast cancer, we evaluated the endocrine effects and toxicity of combined somatostatin analog and dopaminergic therapy in the attempt to suppress both growth hormone (GH) and prolactin (PRL) secretion. The patients' mean age was 63 years (range: 54-77) and the average number of previous treatments was 4.8 +/- 2 (SD). All patients were treated with the somatostatin analog SMS 201-995 (100-200 micrograms s.c. in a.m. and h.s.) and bromocriptine (2.5 mg orally twice a day). During treatment, GH levels following provocative testing (either L-DOPA or insulin-induced hypoglycemia) were suppressed in 7/9 patients. Basal somatomedin-S (Sm-C) levels declined in 6/9 women. Both GH and Sm-C levels decreased in 4 patients, while in the remaining 5 only one of the two parameters was lowered on treatment. PRL secretion (during provocative TRH testing) was almost totally abolished in 8/9 patients. The treatment did not affect circulating levels of FSH, LH, E1, E2, E1-S, T4, T3RU, or cortisol. Seven patients experienced no side effects. Nausea occurred in 3, but was severe enough in only one to require discontinuation of therapy. One patient experienced disease stabilization consisting of less than 50% regression of skin nodules and pleural effusion, a decline in CEA titer, and an improved performance status lasting 7 months. We conclude that combined SMS 201-995 and bromocriptine therapy is safe and frequently suppresses GH and PRL secretion. Its role in the treatment of metastatic breast cancer should be tested in patients with less advanced disease.
Breast Cancer Res Treat 1989 Dec
PMID:Endocrine effects of combined somatostatin analog and bromocriptine therapy in women with advanced breast cancer. 257 6

Serum levels of bioactive lactogenic hormone (BLH), immunoreactive prolactin and growth hormone (ir-PRL and ir-GH) were measured in a group of familial breast cancer patients and their first degree female relatives and compared to those found in normal healthy women. The ratio of BLH to the sum of ir-PRL and ir-GH was slightly but significantly decreased in the familial breast cancer group (P = 0.018 by the Mann-Whitney U test) although there were no significant differences in the levels of BLH, ir-PRL and ir-GH between the two groups. No differences in the levels of the lactogenic hormones could be detected when the pre-menopausal women were considered separately or when 20 women from the familial group were compared to normal controls matched for age, parity, weight and menopausal status. The levels of BLH were highly correlated with the sum of ir-PRL and ir-GH in both the familial breast cancer group and the controls (P less than 0.001 for both groups by Spearman's rank correlation test). These findings are not indicative of the presence of an additional species of bioactive, but not immunoreactive, lactogen in the sera of women with or at high risk of breast cancer. However, the presence of different, but equipotent, forms of lactogen cannot be excluded in these women.
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PMID:Serum bioactive lactogenic hormone levels in women with familial breast cancer and their relatives. 263 55

In order to improve the knowledge of prolactin receptors (PRL-R) in human breast tumors, we studied PRL-R modulation by lactogenic and steroid hormones in the PRL-R rich human breast cancer cell-line, T-47 D. The PRL-R were assayed on a preparation of cell total membranes. We demonstrated an abnormal homologous in vitro regulation of PRL-R. Concentrations of human growth hormone (hGH) greater than 500 ng/ml were required to cause a decrease in PRL-R, with a maximal down-regulation at 2000 ng/ml and for 48 hours. Human placental lactogen (hPL) induced a decrease in PRL-R at concentrations greater than 500 ng/ml but later than hGH; ovine prolactin (oPRL) had no effect on PRL-R. Moreover, we also demonstrated that progestins specifically modulated the expression of PRL-R in T-47D cells: Org 2058, a synthetic progestin induced a statistically significant increase in PRL-R after a twenty-four hour incubation period: this effect was already observed at 10(-9) M and was maximal for 10(-6) and 10(-5) M (186% +/- 3.5% (+/- SEM) for total PRL-R). At 10(-6) M, the stimulation occurred early at three hours and was maximal at twenty-four hours. Conversely estradiol (10(-9) to 10(-6) M), cortisol (10(-9) to 10(-6) M), dexamethasone (10(-9) to 10(-5) M) and RU 486 (10(-9) to 10(-5) M), a progestin and glucocorticoid antagonist, had no effect on PRL-R levels. The Org 2058 PRL-R stimulation was abolished in the presence of RU 486. The abnormal PRL-R down-regulation in the human breast cancer cell-line, T-47D, may contribute a growth advantage to these malignant cells over normal tissues. The progestin PRL-R dependence suggests that high levels of PRL-R may reflect a functional progesterone receptor (Pg-R) and a highly hormone-dependent-phenotype of the tumor. These results support a potential role of PRL in the etiology of breast tumors and may have important implications in the management of human breast cancer.
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PMID:Modulation of prolactin receptors (PRL-R) by lactogenic and steroid hormones in human breast cancer cells in long-term tissue culture (T-47D). 276 10

A receptor for lactogenic hormones (prolactin of several species and human growth hormone) was characterized in crude plasma membrane preparations of adult female rat liver. The binding of 125J-labeled prolactin to receptors was specific, saturable, reversible, and of high affinity (Kd = 0.23 x 10(-10)M). The maximum amount of prolactin specifically bound to liver of untreated female rats was 45 fmol/mg protein, whereas no specific prolactin binding was detected in plasma membrane preparations of adult male or immature rats. With this assay, a specific and reversible binding of ovine prolactin was detected in plasma membrane preparations of 25 human breast cancers, ranging from 2-29% of total activity. The estrogen-, progesterone- and androgen receptor content was determined in the breast cancer specimens using the dextran-coated charcoal method. Specimens with the highest specific prolactin binding showed the lowest steroid receptor concentrations, but no significant correlation between estrogen-, progesterone-, androgen-, and prolactin receptor content and other prognostic factors was observed in our series. We conclude, that steroid and prolactin receptors are expressed independently in human breast cancer.
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PMID:[Comparative studies of prolactin, estrogen, progesterone and androgen receptor levels in human breast cancers]. 284 Jun 18

A food frequency questionnaire was used to estimate and compare the dietary fat and fiber consumption of 94 premenopausal women in Kuopio (rural Finland, where there is a relatively low risk of breast cancer) and 61 American women in New York (where there is a high risk of breast cancer). In keeping with previous reports concerning middle-aged men, both groups had high fat intakes, but the Finnish women had considerably higher fiber intakes (24 +/- 11 vs. 16 +/- 6 g). Serum and breast fluid growth hormone and prolactin levels were compared in 29 of these American women and 24 of the Finnish women. All were healthy and had regular menstrual cycles. Serum growth hormone levels, which were measured by radioimmunoassay, were higher in the Finnish women; all but three of their breast fluids contained detectable growth hormone, frequently at extremely high concentration. In contrast, only 2 of the 29 breast fluids from American women had detectable amounts of growth hormone. Of the Finnish samples, 10 were also measured by an immunoradiometric assay with high specificity for the 22,000-dalton growth hormone molecule; all but 3 had values less than 3.0 ng/ml. Serum and breast fluid prolactin concentrations, which were determined by radioimmunoassay, were no different in the two groups; both groups frequently had considerably higher levels in breast fluid compared with the corresponding serum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diet, serum, breast fluid growth hormone, and prolactin levels in normal premenopausal Finnish and American women. 284 52

The mechanism of action of prolactin in target cells and the role of prolactin in human breast cancer are poorly understood phenomena. The present study examines the effect of human prolactin (hPRL) on the synthesis of unique proteins by a human breast cancer cell line, T-47D, in serum-free medium containing bovine serum albumin. [35S]Methionine-labeled proteins were analysed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis and fluorography. Treatment of cells with hPRL (1-1000 ng/ml) and hydrocortisone (1 microgram/ml) for 36 h or longer resulted in the synthesis and secretion of three proteins having molecular weights of 11,000, 14,000, and 16,000. Neither hPRL nor hydrocortisone alone induced these proteins. Of several other peptide hormones tested, only human growth hormone, a hormone structurally and functionally similar to hPRL, could replace hPRL in causing protein induction. These three proteins were, therefore, referred to as prolactin-inducible proteins (PIP). Each of the three PIPs was purified to homogeneity by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and specific antibodies were generated to them in rabbits. By immunoprecipitation and immunoblotting (Western blot) of proteins secreted by T-47D cells, it was demonstrated that the three PIPs were immunologically identical to one another. In addition, the 16-kDa and 14-kDa proteins (PIP-16 and PIP-14), and not the 11-kDa protein (PIP-11), incorporated [3H]glycosamine. Furthermore, 2-deoxyglucose (2 mM) and tunicamycin (0.5 micrograms/ml), two compounds known to inhibit glycosylation, blocked the production of PIP-16 and PIP-14, with a concomitant increase in the accumulation of PIP-11. These results indicate PIP-16 and PIP-14 are glycosylated variants of PIP-11. Finally, in vitro translation of poly(A)+ messenger RNA followed by immunoprecipitation revealed a 12.5-kDa protein, possibly the precursor form of PIPs. In addition, T-47D cells treated with hPRL plus hydrocortisone contained 10-fold more mRNA for PIPs than control cells, suggesting that the hormones' action is at the level of gene expression. Our finding represents a first demonstration of prolactin regulation of gene expression in human target cells. The human breast cancer cells, T-47D, appear to be an excellent model to afford future studies on the molecular action of prolactin and on the possible role of prolactin in human breast cancer.
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PMID:Prolactin-inducible proteins in human breast cancer cells. 286 72

Human breast cancer cells secrete and have membrane receptors for insulin-like growth factor I (IGF-I), a growth hormone-dependent peptide that stimulates cell replication. However, little is known about plasma concentrations of IGF-I in breast cancer patients. Plasma IGF-I levels are decreased in malnutrition, decline with advancing age, and are influenced by estrogen. We evaluated the effect of the antiestrogen agent tamoxifen on plasma IGF-I in 32 ambulatory breast cancer patients. Treatment with tamoxifen was associated with lower concentrations of plasma IGF-I (0.48 +/- 0.3 unit/ml in treated versus 1.03 +/- 0.6 units/ml in nontreated patients, P less than 0.01). However, patients treated with tamoxifen did not differ from nontreated patients in age, menopause, duration since diagnosis, metastatic disease, recent weight loss, or measures of nutritional status. We conclude that tamoxifen therapy results in a reduction of plasma IGF-I concentration. We speculate that the antitumor action of tamoxifen in breast cancer is due in part to suppression of IGF-I.
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PMID:Effect of tamoxifen on plasma insulin-like growth factor I in patients with breast cancer. 292 27

A 24 hr incubation of T-47D human breast cancer cells with R5020, a synthetic progestin, resulted in a 200-250% increase in the specific binding of human growth hormone (hGH) and epidermal growth factor (EGF) by these cells. This effect was specific for progestins in that similar responses were observed with progesterone, medroxyprogesterone acetate and ORG 2058 but no significant increases in hGH or EGF binding were observed in cells incubated with testosterone, estradiol or hydrocortisone. Increased binding was due to an increase in the concentration of receptors (hGH, control = 6,490 +/- 500, progestin treated = 13,180 +/- 3,270 sites/cell; EGF, control = 33,380 +/- 7,410, progestin treated = 67,460 +/- 20,330 sites/cell) while the affinity constants for the hormone-receptor interactions were unchanged by progestin treatment. The specific binding of insulin, calcitonin, transferrin and concanavalin A was unaffected by these treatments. It is concluded that expression of hGH and EGF receptors in this breast cancer cell line is regulated by progestins.
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PMID:Regulation of growth hormone and epidermal growth factor receptors by progestins in breast cancer cells. 299 26

Although polyamines are important in regulating proliferation of mammalian cells, their role in hormone induction of cell growth has not been delineated. In the estradiol-responsive human breast cancer cell line, T-47D clone 11, estradiol (10(-10) M) was able to stimulate cell proliferation and the activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, blocked the estradiol-induced cell proliferation and ODC activity. Exogenous addition of putrescine, the natural product of ODC, rescued the inhibitory effect of DFMO. In addition, DFMO abolished the estradiol-induced growth of several other estrogen-responsive human breast cancer cell lines but did not affect the growth of hormone-independent cell lines. Further, a serum factor was found to be required for estradiol to exert its effect. To gain insight into the nature of this and possibly other extrinsic factors involved, the effect of estradiol on the proliferation of T-47D cells transplanted into athymic nude mouse was evaluated. In this in vivo system, estradiol alone produced only moderate growth of the human breast tumor. The simultaneous transplantation of a prolactin (PRL)- and growth hormone (GH)-secreting rat pituitary tumor or normal rat pituitary glands at a different site dramatically potentiated the effect of estradiol on the growth of the breast tumor xenograft. Purified PRL or GH were without effect, indicating that the active pituitary factor is neither PRL nor GH. Further, conditioned medium from rat pituitary tumor cells potentiated the mitogenic effect of estradiol on T-47D and several other estrogen receptor-positive human breast cancer cell lines in vitro under serum-free condition. In conclusion, we have identified both intrinsic (polyamines) and extrinsic (pituitary/serum) factors that are importance for estrogen to exert its mitogenic action. The next goal will be to elucidate the mechanisms of action of these molecules in the modulation of estrogen action.
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PMID:Intrinsic and extrinsic factors in estrogen action in human breast cancer: role of polyamines and pituitary factors. 308 72


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