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)

The somatostatin analogue octreotide (SMS 201-995) inhibits secretion and growth of certain tumor cells, and current efforts are directed toward the elucidation of its mode of antiproliferative action. In this study, the effect of octreotide on the growth of ZR-75-1 human breast cancer cells has been characterized in immunodeficient nude mice and in cell culture. These results have been related to the expression of somatostatin receptors in vivo and in vitro. Continuous infusion of 10 micrograms/kg/h of octreotide yielded plasma levels of 5.7 ng/ml and elicited highly significant growth inhibitory effects on solid ZR-75-1 breast tumors in nude mice. After 2 and 4 weeks of treatment, tumor volumes in the octreotide group were 39.1 and 36.7% of those of control animals treated with vehicle, respectively. Autoradiographic studies demonstrated that 8 of 12 ZR-75-1 tumors studied were somatostatin receptor positive. When ZR-75-1 tumor cells were exposed in vitro to nanomolar concentrations of octreotide, a dose-dependent inhibition of cell growth was observed in the presence of 5% fetal calf serum or under serum-free conditions using epidermal growth factor, insulin-like growth factor type I, or insulin as growth stimulus. In parallel receptor-binding experiments, ZR-75-1 cells were shown to express specific high-affinity somatostatin receptors (Kd value = 0.9 nM, Bmax = 6000 sites/cell). From these experiments, we conclude that octreotide is a powerful inhibitor of ZR-75-1 tumor cell growth in nude mice and in culture. This inhibitory action of octreotide and the presence of somatostatin receptors on ZR-75-1 tumor cells in vitro and in vivo suggest a direct, somatostatin receptor-mediated effect of octreotide.
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PMID:Antiproliferative effects of the somatostatin analogue octreotide (SMS 201-995) on ZR-75-1 human breast cancer cells in vivo and in vitro. 132 89

Plasma levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein I (IGFBP-I) were measured in fasting blood samples obtained from 16 postmenopausal breast cancer patients before and during tamoxifen treatment for 1 to 6 months. Tamoxifen suppressed total plasma IGF-I by a mean of 28.5% (P less than 0.001) but elevated plasma IGFBP-I by a mean value of 78% (P less than 0.001). Changes in plasma levels of growth hormone, insulin, or insulin C-peptide were not observed. These findings suggest that tamoxifen exerts its influence on plasma IGF-I and IGFBP-I by mechanisms other than those known to regulate the plasma levels of these peptides, primarily growth hormone and insulin, respectively. A dual effect suppressing plasma IGF-I and elevating plasma IGFBP-I suggests that tamoxifen may have a significant influence on endocrine and possibly paracrine delivery of IGF-I to breast cancer cells in vivo.
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PMID:Influence of tamoxifen on plasma levels of insulin-like growth factor I and insulin-like growth factor binding protein I in breast cancer patients. 138 Aug 89

Tamoxifen treatment of women with advanced breast cancer has previously been reported to reduce plasma insulin-like growth factor-type I (IGF-I) concentrations. In this study we have examined the effect of treatment with Tamoxifen, medroxyprogesterone acetate (MPA) or 4-hydroxyandrostenedione (4-OHA) on plasma IGF-I and IGF-II concentrations. As IGF-binding proteins (IGFBPs) can modulate the biological effects of IGF-I, plasma IGFBP-I levels were also measured. Treatment with Tamoxifen for 2 weeks resulted in a small, but significant, decrease in IGF-I levels, but increase in the plasma concentration of IGFBP-I. In contrast, treatment with MPA increased levels of IGF-I, but significantly reduced plasma IGFBP-I concentrations. Treatment with 4-OHA had no significant overall effect on plasma IGF-I or IGFBP-I levels, although changes were detected for some subjects. Plasma IGF-II concentrations were not altered by treatment with Tamoxifen, MPA or 4-OHA. It is concluded that although treatment with Tamoxifen or MPA produced significant changes in plasma IGF-I concentrations, any physiological effects of such changes are likely to be modulated by the corresponding alterations in plasma IGFBP-I concentrations.
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PMID:The effect of endocrine therapy with medroxyprogesterone acetate, 4-hydroxyandrostenedione or tamoxifen on plasma concentrations of insulin-like growth factor (IGF)-I, IGF-II and IGFBP-1 in women with advanced breast cancer. 138 3

Human breast cancer cells have been recently reported to produce endothelin (ET) 1. To investigate the potential regulation of ET production in breast cancer cells, we have measured the release of ET-like immunoreactivity from the T47D cell line in response to various paracrine/endocrine factors. Bombesin (0.1 microM) and cortisol (1 microM) stimulated maximal respective increases in IR-ET release to 580 and 369% of basal values after 6 h. The responses to cortisol and bombesin were additive. The response to bombesin was dose dependent with a median effective dose around 1 nM and was inhibited by the receptor antagonist [Leu13-psi-CH2NH-Leu14]bombesin. Pretreatment of T47D cells with pertussis toxin had no effect on bombesin-induced inositol lipid hydrolysis but inhibited ET-like immunoreactivity release in response to bombesin in the presence of glucocorticoid, by 56%. ET-1 (10 nM) and insulin-like growth factor (10 ng/ml) stimulated modest separate increases in DNA synthesis in human breast fibroblasts of 35 and 71%, respectively, but together exhibited a strong synergistic response to 905% of control values. This in vitro study demonstrates the potential for bombesin and glucocorticoid to regulate ET production in human breast cancer cells, which may in turn have a paracrine influence on neighboring stromal cell function.
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PMID:Bombesin and glucocorticoids stimulate human breast cancer cells to produce endothelin, a paracrine mitogen for breast stromal cells. 155 Nov 9

Currently there is much interest in the role that growth factors may play in the development of human breast tumours. We have shown previously that growth factors secreted by breast tumours may influence the activity of oestradiol hydroxysteroid dehydrogenase, the enzyme which catalyses the interconversion of oestrone (E1) and oestradiol. As the formation of E1 from its sulphate (E1S) by oestrone sulphatase may be quantitatively more important than production from androstenedione via aromatase, we have studied the effect of insulin-like growth factor-1 (IGF-I) and basic fibroblast growth factor (bFGF) on oestrone sulphatase activity in the hormone-dependent MCF-7 and the hormone-independent MDA-MB-231 breast cancer cell lines. In both these cell types, bFGF (1-200 ng/ml) and IGF-I (25-200 ng/ml) significantly stimulated oestrone sulphatase activity in a dose-dependent manner (by 8-60%) after 48 h. Additionally, cycloheximide significantly inhibited (by 90-120%) this stimulation of oestrone sulphatase activity by the two growth factors in both MCF-7 and MDA-MB-231 cells. Basal oestrone sulphatase activity was higher in the oestrogen receptor, ER-ve MDA-MB-231 cells than in the ER + ve MCF-7 breast cancer cells. We conclude that these growth factors, believed to be secreted by breast tumours, may induce enzymes of oestrogen synthesis and hence increase local production of oestrogens.
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PMID:Modulation of oestrone sulphatase activity in breast cancer cell lines by growth factors. 156 28

Earlier physical maturity in girls, involving an earlier and more marked growth hormone spurt and also an earlier menarche, is a marker of subsequent higher risk to breast cancer. Based on the results of recent research, it is postulated that interaction between growth hormone, insulin-like growth factor and sex steroids at an earlier age, has a major role in stimulating not only linear growth but also precocious proliferative activity in the breasts of adolescent girls. This may promote carcinogenesis in a susceptible mammary epithelium and could partly account for the rising breast cancer mortality rate among both Japanese and Western women.
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PMID:Breast cancer risk in Japanese women with special reference to the growth hormone-insulin-like growth factor axis. 157 84

Interleukin-6 (IL-6) causes an epithelial to fibroblastoid conversion and an increase in the motility of human ductal breast carcinoma cell lines ZR-75-1 and T-47D. Although IL-6 decreases DNA synthetic activity in these cell lines, the IL-6-induced alterations in cell shape and motility occur independently of inhibition of DNA synthesis per se. Whereas tumor necrosis factor alpha (TNF-alpha) inhibits DNA synthesis in T-47D cells, it does not cause an epithelial-fibroblastoid conversion or other major morphological changes and does not increase cell motility; TNF-alpha rapidly lyses a majority of ZR-75-1 cells. Furthermore, the DNA synthesis inhibitors 5-fluoro-2'-deoxyuridine (FUDR) and methotrexate (MTX) also do not cause effects mimicking the action of IL-6 on cell structure and motility. Transforming growth factors alpha and beta 1, acidic and basic fibroblast growth factors, epidermal growth factor, and insulin-like growth factor-1 (TGF-alpha, TGF-beta 1, aFGF, bFGF, EGF, and IGF-1) have little or no effect on breast cancer cell morphology, which serves to exclude the possibility that the IL-6-induced changes are a consequence of induction of these growth factors by IL-6. 12-O-tetradecanoyl phorbol-13-acetate (TPA) but not 8-bromoadenosine 3',5'-cyclic monophosphate (Br-cAMP) induces changes in the morphology and associative behavior of ZR-75-1 cells that are similar but not identical to those caused by IL-6. The TPA-induced alterations are not blocked by anti-IL-6 neutralizing antibodies; staurosporine inhibits the TPA-induced cell alterations but not those induced by IL-6. IL-6 and TPA used together have a phenotypic effect that greatly exceeds that of either agent alone and results in extensive cell scattering in less than 1 day. These findings are consistent with the hypothesis that IL-6 and TPA induce similar morphological changes and cell scattering via independent pathways.
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PMID:Interleukin-6 and 12-O-tetradecanoyl phorbol-13-acetate act synergistically in inducing cell-cell separation and migration of human breast carcinoma cells. 165 54

We have studied the regulation by estradiol of the mannose-6-phosphate (Man-6-P)/insulin-like growth factor-II (IGF-II) receptor concentration in different breast cancer cell lines. The mRNA level was assayed by Northern blot using the H5.1 cDNA probe. The protein level was assayed by Western ligand blot, by binding saturation with [125I]procathepsin-D on total membrane preparations, and by immunoprecipitation of 35S-labeled proteins. In three estrogen receptor-positive cell lines (MCF7, T47D, and ZR75-1), estradiol specifically decreased the steady state level of the Man-6-P/IGF-II receptor protein and mRNA. Moreover, in different cell lines and in primary culture of normal mammary cells, the secretion of procathepsin-D was inversely correlated with the level of Man-6-P/IGF-II receptor protein and mRNA. We conclude that estradiol down-regulates the Man-6-P/IGF-II receptor in breast cancer cells. Since two of its ligands, procathepsin-D and IGF-II, are induced by estrogen, we propose that the Man-6-P/IGF-II receptor becomes saturated after estrogen treatment. This model might explain the previously described estrogen-induced secretion of procathepsin-D and other lysosomal proenzymes routed by the same transport system.
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PMID:Estradiol down-regulates the mannose-6-phosphate/insulin-like growth factor-II receptor gene and induces cathepsin-D in breast cancer cells: a receptor saturation mechanism to increase the secretion of lysosomal proenzymes. 165 43

Using molecular hybridization, ligand blotting and immunoprecipitation, our studies were designed to identify the insulin-like growth factor binding proteins (IGFBPs) produced by human breast cancer cells in culture and evaluate their regulation by estradiol (E2) and polyamines (PA). We demonstrate that the hormone-dependent MCF-7 and -independent BT-20 cell lines express the mRNA for IGFBP-2 (1.7 kb) and secrete this BP (31 kDa) in the conditioned medium. In contrast, the hormone-independent MDA-MB-231 cell line does not express the IGFBP-2 gene, while synthesizing and secreting IGFBP-1. E2 administration (10(-9) M) did not significantly influence IGFBPs secretion in MCF-7 cells. Addition of alpha-difluoromethylornithine (DFMO, 4 mM), an inhibitor of PA biosynthesis, consistently lowered IGFBP-2 mRNA in the MCF-7 and BT-20 cell lines and IGFBP-1 mRNA in MDA-MB-231 cells. Surprisingly, however, this compound either did not influence IGFBPs secretion in MCF-7 cells or actually increased their secretion in the BT-20 and MDA-MB-231 cell lines. PA involvement in IGFBPs production by breast cancer cells is complex and may involve differential regulation of transcriptional and post-translational events.
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PMID:Identification and regulation of insulin-like growth factor binding proteins produced by hormone-dependent and -independent human breast cancer cell lines. 171 94

The effects of estrogens and tamoxifen were analyzed on estrogen receptor-positive human breast cancer (MCF-7) transplanted into athymic nude mice. It was found that (1) the tumor growth and the proportion of 3H-thymidine-labeled cells were significantly increased in the 17 beta-estradiol dipropionate (E2) group, but significantly decreased in the tamoxifen (TAM) group with respect to the control group, and (2) the tumor content of insulin-like growth factor-1 (IGF-1) and the rate of IGF-1-positive cells were significantly lower in the E2 group, but significantly higher in the TAM group than in the control group. It was concluded that the tumor content of IGF-1 and the proportion of IGF-I-positive cells were inversely correlated to the tumor growth and the 3H-thymidine labeling index in vivo.
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PMID:Effects of hormones on tumor growth and immunoreactive insulin-like growth factor-1 of estrogen receptor-positive human breast cancer (MCF-7) transplanted in nude mice. 175 78


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