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

We have examined the interaction of dexamethasone with the ZR75-1 human breast cancer cell line to determine if glucocorticoids might directly inhibit growth of breast cancer cells. Growth of these cells in serum-free medium was stimulated significantly by physiological concentrations of insulin (0.1 to 1.0 nM). Pharmacological concentrations of dexamethasone (10 nM) reduced cell number below that found in controls and nearly abolished the effect of insulin after several days in culture. Thymidine and uridine, but not leucine, incorporation into macromolecules or acetate incorporation into fatty acids were similarly inhibited by dexamethasone in the presence of absence of insulin. Dexamethasone did not inhibit insulin effects by altering insulin receptor affinity or concentration, as determined by Scatchard analyses of insulin binding. Net thymidine uptake into the trichloroacetic acid-soluble fraction of the cell was stimulated by insulin and inhibited by dexamethasone also inhibited thymidine kinase activity multiple potential sites of glucocorticoid action that directly oppose the effects of insulin. They also suggest that glucocorticoids have a direct inhibitory effect on proliferation of human breast cancer cells, which may help explain breast tumor regression following pharmacological glucocorticoid therapy.
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PMID:Direct inhibition of growth and antagonism of insulin action by glucocorticoids in human breast cancer cells in culture. 44 41

To investigate further the molecular mechanisms of progestin regulation of human breast cancer cell growth, we studied the effect of progestins on expression of the protooncogene c-jun and other members of the jun family, jun-B and jun-D, in T-47D human breast cancer cells. The progestin medroxyprogesterone acetate (MPA) increased c-jun mRNA levels in a time- and dose-dependent fashion. Maximal effects were seen after 3 h of treatment with 10-100 nM MPA. Under these conditions, the c-jun mRNA was increased 5.4-fold above the control level. Although the c-jun mRNA level was increased by cycloheximide alone, a further 2.4-fold increase was seen when the cells were treated with MPA in the presence of cycloheximide. The p39 c-jun protein was also increased 3.8-fold by this treatment. Maximum levels of p39 c-jun protein were achieved 9 h after treatment, and this level was maintained for at least 24 h. Dexamethasone and dihydrotestosterone did not increase the p39 c-jun protein level under these conditions. However, MPA treatment of T-47D cells resulted in a 55% decrease in overall AP-1 activity, as measured by transient transfection of an AP-1-regulated chloramphenicol acetyltransferase reporter gene. These effects were all reversible by cotreatment with a 10-fold higher concentration of the antiprogestin RU 486. MPA decreased jun-B mRNA levels 50% 1 h after treatment in T-47D cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of c-jun and jun-B by progestins in T-47D human breast cancer cells. 144 15

Malignant cystosarcoma phylloides (CP) is a relatively rare cancer of the breast. A CP tumor was processed as part of a tumor acquisition, propagation, and preservation program in patient biotherapy. Two tissue culture cell lines were developed from this tumor, one directly from the biopsy, another from a xenograft tumor grown in athymic mice. The two cell lines were similar in character. There was strong immunochemical reactivity with antibodies to vimentin, type I collagen, and type III collagen. There was no reactivity with antibodies to cytokeratin and epithelial membrane antigen. Both cell lines were aneuploid, clonogenic in soft agar, and tumorigenic in nude mice. 5 alpha-dihydrotestosterone and thyroxine added to the culture medium stimulated growth, while testosterone, 17 beta-estradiol, and 4-hydroxytamoxifen were without effect. Dexamethasone and cortisol were inhibitory at high doses (10(-6) M). Dibutyryl cyclic AMP, theophylline, and vitamin C were all inhibitory. The biopsy contained tumor-infiltrating lymphocytes which proliferated in cultures containing interleukin 2. The expanded lymphocytes were activated T cells which had the capacity to lyse tumor cells. These results suggest possibilities in the therapy of cystosarcoma phylloides involving vitamin C, certain hormones, and tumor-infiltrating lymphocytes.
Breast Cancer Res Treat 1990 Dec
PMID:Cultured breast cystosarcoma phylloides cells and applications to patient therapy. 196 88

Epidermal growth factor (EGF) is thought to be important in normal mammary development. The presence of EGF receptors in breast cancer cells suggests that it may also have a role in regulating growth of tumors of the human breast. Using a complementary DNA probe for the human EGF precursor we have examined expression of this gene in a series of human breast cancer cells in long term culture. The T-47D cell line demonstrated the highest level of EGF mRNA. EGF expression was not detectable in the MCF-7, BT 20, or HBL 100 cell lines. Surprisingly, in both T-47D and ZR 75 cells, pretreatment with progestins which exert antiproliferative effects under the conditions used increased EGF mRNA levels approximately 6-fold above untreated controls. This effect, demonstrable with as little as 0.1 nM of medroxyprogesterone acetate, was apparent as early as 12 h after addition of progestin and was reversed with the antiprogestin RU 486. Dexamethasone, estradiol, and dihydrotestosterone had no effect on EGF expression in T-47D cells. There was no evidence that the increased levels of EGF mRNA were due to gene amplification. Immunoprecipitation of biosynthetically labeled T-47D conditioned medium with antibodies to human EGF and EGF-precursor revealed the presence of both Mr 40,000 and 18,000 products. Fully processed Mr 6,000 EGF was not detectable in either conditioned medium or cell lysate. These data provide unequivocal evidence for the expression of the EGF gene in some human breast cell lines.
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PMID:Epidermal growth factor gene expression in human breast cancer cells: regulation of expression by progestins. 326 Aug 16

Cytosolic casein kinase type II activity has been identified in MCF-7 and MDA-MB-231 human breast cancer cells heterotransplanted into athymic nude mice. Sephacryl S-300 chromatography of MCF-7 and MDA-MB-231 tumor cytosols revealed a major peak of casein kinase activity with an estimated molecular weight of 150,000. This peak was further characterized and optimal conditions for breast tumor casein kinase activity were established. Polylysine (10 micrograms) acted as a potent stimulator with casein as the phosphate acceptor protein. This enzyme used both ATP and GTP as phosphate donors and the Km for GTP was 10 microM. The rate of phosphorylation with increasing concentrations of [gamma-32p]GTP revealed typical Michaelis-Menten kinetics and Vmax was approached at a concentration of 30 microM GTP. MgCl2 stimulated enzyme activity at concentrations between 10-20 mM. Quercetin, a bioflavonoid, inhibited casein kinase type II activity in a dose dependent manner. MCF-7 (hormone-dependent) human breast cancer cells (2-3 X 10(6)) were inoculated into the mammary fat pads of nude mice, supplemented with a 0.5 mg estradiol pellet. To determine the influence of various regulatory agents on casein kinase activity in vivo, tumor-bearing mice were treated for five days with estradiol, progesterone, dexamethasone or tamoxifen. Casein kinase type II was partially purified by gel filtration on a Sephacryl S-300 column and assayed in the presence of polylysine and casein. Dexamethasone treatment significantly decreased casein kinase II activity in MCF-7 tumors, which are receptor-positive for estrogen, androgen and glucocorticoid receptors.
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PMID:Characterization and hormonal regulation of casein kinase II activity in heterotransplanted human breast tumors in nude mice. 348 45

6 cases of breast cancer in women aged 19-45 years are reported. All underwent radical mastectomy (5 had presented with lymph node involvement) and were then treated with combined estrogen-gestagen preparations (Lyndiol, Lutestral, Dectancyl). After 1-4 years there is no evidence of local recurrence, regional lymph node involvement, or distant metastases. These encouraging results have led the authors to continue research into the possibility of slowing down the spread of metastases in young women by the use of estrogen-gestagen combinations administered in contraceptive-level dosage.
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PMID:[Remarks about some still young patients treated with the gestagen-estrogen association immediately after radical treatment of malignant tumors of the breast]. 409 66

To assess the value of high-dose dexamethasone therapy in preventing the gastrointestinal (GI) side effects of chemotherapy, a randomized double-blind study was conducted in women receiving outpatient therapy for breast cancer. Single-dose dexamethasone sodium phosphate (10 mg) or placebo was administered intravenously in 57 trials in 22 women immediately before chemotherapy. Questionnaires (administered before therapy and 24 hours later) were compared for evidence of nausea, vomiting, and anorexia produced by chemotherapy. No GI intolerance to chemotherapy was noted in 24 (83%) of the 29 dexamethasone trials v 16 (57%) of the 28 placebo trials. Dexamethasone trials produced the following results: no side effects in 50% (14/29), insomnia the night after chemotherapy in 21% (6/29), an increase in energy levels in 24% (7/29), and an improvement in mood in 14% (4/29). High-dose dexamethasone therapy has useful application in alleviating the emetic effects of cancer chemotherapy.
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PMID:Antiemetic efficacy of dexamethasone therapy in patients receiving cancer chemotherapy. 634 9

Activity of secreted plasminogen activator (PA) by ZR-75-1 human breast cancer cells in culture is shown to be altered by the addition of physiologically relevant concentrations of the hormones 17 beta-estradiol (E2), insulin, and dexamethasone. After 48 h, E2 stimulated PA activity 6-fold at concentrations as low as 10(-12) M. This stimulation was prevented by the addition of actinomycin D and cycloheximide. The antiestrogen tamoxifen reduced estrogen stimulation of PA, but had slight stimulatory effects on PA secretion by itself. Insulin (5 X 10(-10) M) induced a 2-fold increase in PA activity. Effects of insulin and E2 were additive, suggesting independent sites of control of PA production. Dexamethasone (10(-8) M) decreased PA activity by 20%, but did not inhibit cell growth at the concentration tested. These data suggest that secreted PA activity is differentially regulated by hormones and that effects of PA and growth do not occur in parallel.
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PMID:Hormonal control of plasminogen activator secretion in ZR-75-1 human breast cancer cells in culture. 637 Jun 66

The effects of steroid hormones on the colony forming activity of a human breast cancer cell line (MCF-7) were studied. Endrogeneous estrogens in the fetal calf sera used for culture were deprived using the dextran-coated charcoal, and only batches of E2-deprived serum were chosen with which there was a significant increase in the plating efficiency after E2 (estradiol-17 beta, 10(-8) M) treatment. Progesterone showed little effect on the growth of the cells. not being influenced by the addition of E2. The capacity of the cells to form colonies was stimulated by androgens (5 alpha-dihydrotestosterone, testosterone) only in the absence of E2. Dexamethasone had suppressive effects regardless presence of E2. Thus, MCF-7 cells showed variable responses to these steroid hormones, although the cells have specific receptors to the hormones. This colony formation method of MCF-7 cells may be a useful model system for the study of hormonal and non-hormonal anti-cancer agents.
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PMID:[Evaluation of steroid hormone sensitivity of human breast cancer cells in culture (MCF-7) by a colony formation method]. 687 Mar

The effects of estradiol (E2) on two cloned sublines derived from the T47D human breast cancer cell line have been studied in vitro. Cell proliferation was evaluated by DNA assay, cell counts, and thymidine incorporation. The rate of synthesis of proteins released into the cell culture medium was assayed by [35S]methionine incorporation and polyacrylamide gel electrophoresis, followed by fluorography. In clone 11, which contains estrogen and progesterone receptors, estradiol (1 pM-1 nM) stimulated cell proliferation 2- to 5-fold after a lag period of 6 days. Maximal stimulation was observed with 1% or 3% fetal calf serum and without added insulin. The effect of E2 was biphasic, since the growth rate was stimulated for E2 concentrations less than 10 nM and then progressively inhibited for higher concentrations. Dexamethasone, dihydrotestosterone, progesterone, and R5020 (at 1 nM or 1 microM) did not modify cell growth. The antiestrogen Tamoxifen (1 microM) inhibited the E2-induced stimulation and decreased the growth of control cells. Estrogen also stimulated 2- to 3-fold the synthesis of approximately 60K molecular weight dalton proteins which were released into the medium. This effect was seen as early as 1 day of E2 treatment, and a plateau of stimulation was reached with 0.1 nM E2. By contrast, in clone 8, which contains low concentrations of estrogen and progesterone receptors, E2 had no effect on cell growth and stimulated slightly the synthesis of a 55K protein. These results demonstrate that E2 is able to directly stimulate the proliferation of human epithelial breast cancer cells after having stimulated the synthesis of approximately 60,000 dalton proteins released into the medium.
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PMID:Estrogens stimulate cell proliferation and induce secretory proteins in a human breast cancer cell line (T47D). 704 50


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