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

Human breast cancer MCF-7 cells containing estrogen receptor are killed by transforming growth factor-beta (TGF-beta). We isolated variants of MCF-7 highly resistant to TGF-beta. Variants ES-1 and ES-4 were cloned, and the growth of ES-1 and ES-4 was found to be inhibited by estradiol, whereas estradiol stimulated the growth of the parental MCF-7 cells. ES-1 cells contained about 2-fold higher level of estradiol receptor than MCF-7 cells. Addition of estradiol to the culture medium for MCF-7 and the variant changed the expression of several secreted proteins. The repertoire of secreted proteins was markedly altered in the variant. Polypeptides of molecular weight 52,000 (52 K), 65 K and 160 K were increased about 10- to 50-fold in both estradiol-treated MCF-7 and ES-1 cells. Polypeptide of 130 K was decreased in estradiol-treated ES-1 cells while this polypeptide was increased about 4-fold in estradiol-treated MCF-7, as compared with untreated MCF-7. Polypeptide of 100 K was specifically secreted in ES-1 whether or not estradiol was present, but there appeared to be no significant amount of the 100 K protein in MCF-7. The estradiol-hypersensitive phenotype is discussed in relation to its aberrant expression of secreting proteins.
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PMID:Estrogen inhibits the growth of MCF-7 cell variants resistant to transforming growth factor-beta. 312 8

A number of recombinant cytokines believed to regulate normal hematopoiesis are now being used in cancer treatment protocols to reduce the myelosuppressive toxicity of intensive chemoradiotherapy regimens. It is widely assumed that such cytokines are relatively specific for hematopoietic cells, although some cell lines derived from a variety of non-hematopoietic human tumors can respond to some of these factors. However, relatively little is known about their ability to stimulate (or inhibit) the proliferation of freshly isolated normal or malignant non-hematopoietic cells. We have used a serum-free culture medium that selectively supports the growth of human breast epithelial cells (HBEC) obtained directly from normal or malignant tissue samples to evaluate potential stimulatory or inhibitory effects of eight cytokines: granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, Steel factor, interleukin-2, interleukin-3, interleukin-6, transforming growth factor-beta and macrophage inflammatory protein-1 alpha, on these cells cultured both in the presence of epidermal growth factor, a potent stimulator of HBEC growth, and in its absence. HBEC growth was assessed after 7 and 14 days using the tetrazolium-dye reduction assay. Potential effects on the well studied MCF-7 breast cancer cell line, cultured under the same conditions, were also investigated. None of the cytokines (which were tested over a wide range of concentrations) had any modulating effect on the growth of normal or malignant HBEC under the conditions used with the exception of transforming growth factor-beta, which was consistently and significantly inhibitory.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of effect of hematopoietic growth factors on human breast epithelial cell growth in serum-free primary culture. 751 1

Estrogenic stimulation is a potent risk factor for the development of uterine cancer. More recently, analysis of patients in prospective breast cancer trials have established that tamoxifen also increases uterine cancer risk. In this report, uteri of oophorectomized rats were examined to ascertain the effects of estrogen and tamoxifen on the uterine induction of two isoforms of transforming growth factor-beta (TGF-beta). In contrast to studies of cells derived from breast epithelium, our studies reveal that both estrogen and tamoxifen increase immunoreactive TGF-beta. These changes were particularly pronounced in the endometrial stroma. Effects of progesterone also were examined and found to be distinct and relatively restricted to the glandular epithelium. These studies indicate that, in the uteri of oophorectomized rats, tamoxifen exerts estrogen-like effects on a peptide previously implicated in the control of cellular growth and differentiation. We hypothesize that induction of TGF-beta isoforms may be an important mediator of both estrogen- and tamoxifen-induced proliferative disorders in the uterus.
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PMID:Analogous tamoxifen and estrogen effects on transforming growth factor-betas 1 and 2 in the rat uterus. 757 6

The aim of this study was to examine whether changes in growth factor or cytokine expression could be responsible for the growth inhibitory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the human breast cancer MCF-7 cell line. Treatment of MCF-7 cells with 10 nM TCDD for 7 days reduced the cell growth to 60% of control; this effect was partly abolished by cotreatment of the cells with 100 nM 17 beta-estradiol (E2). The inhibition of cell growth by TCDD was accompanied by an enhanced secretion of transforming growth factor-beta (TGF-beta) and the TGF-beta content in cell culture supernatants was 2-fold higher than in controls. Using reverse transcription polymerase chain reaction (RT-PCR), the effect of TCDD on the expression of TGF-beta isoforms, transforming growth factor-alpha (TGF-alpha), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) was investigated. It was demonstrated that incubation with 1, 10 and 100 nM TCDD for 24 h increased mRNA levels of TGF-alpha, TNF-alpha and IL-1 beta. The strongest effect was found on IL-1 beta, the mRNA level of which was dose-dependently increased. TCDD had a minor effect on TGF-alpha and TNF-alpha mRNA. The mRNA levels were significantly increased after treatment with 10 and 100 nM TCDD. The mRNA expression of TGF-beta 1 and TGF-beta 2 was unchanged, whereas the TGF-beta 3 mRNA level was enhanced 2 to 3-fold after TCDD treatment. From the results, we suggest that TCDD-induced growth inhibition in MCF-7 cells is related to the growth inhibitory action of a set of growth factors and cytokines which have a contextual action on MCF-7 cell proliferation.
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PMID:Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on growth factor expression in the human breast cancer cell line MCF-7. 775 87

Women with "apocrine" breast cysts (usually having intracystic Na/K < 3) may have a higher risk of developing breast cancer than women with breast cysts lined by flattened epithelium (usually having intracystic Na/K > 3). In this study the concentrations of basic fibroblast growth factor (bFGF), a potent mitogen, and transforming growth factor-beta 2 (TGF-beta 2), which exerts a growth inhibitory effect on epithelial cell types, were measured in breast cyst fluid and their relationship studied. Both growth factors were measured by "sandwich" enzyme immunometric assays. The concentrations of both bFGF and TGF-beta 2 were significantly higher (P < 0.001) in the Na/K > 3 group (median 444 fmol/L, range: < 56 fmol/L-7,890 fmol/L, n = 23 and median 1,776 pmol/L, range: 20.4 pmol/L-5,000 pmol/L, n = 19 respectively) than in the Na/K < 3 group (median < 56 fmol/L, range: < 56 fmol/L-2,722 fmol/L, n = 21 and median 176 pmol/L, range: 12 pmol/L-1,940 pmol/L, n = 23 respectively). Significantly positive correlations were found between bFGF and TGF-beta 2 (rS = 0.496, n = 37, P = 0.002), bFGF and Na/K (rS = 0.599, n = 44, P < 0.001) and TGF-beta 2 and Na/K (rS = 0.521, n = 42, P < 0.001). The significantly higher concentrations of the growth inhibitory TGF-beta 2 in the Na/K > 3 cyst group may provide an explanation for the lower risk of breast cancer which has been observed in this group of women. The role of bFGF in mammary carcinogenesis is unclear as lower levels of this growth factor are present in breast cancer tissue and breast cancer cell lines than in normal breast tissue and cell lines. The positive correlation between bFGF and TGF-beta 2 may indicate regulation by a common factor or that one of these growth factors may regulate the production of the other. This is the subject of further study.
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PMID:Relationship between basic fibroblast growth factor and transforming growth factor-beta 2 in breast cyst fluid. 785 41

Angiogenesis is a major new prognostic factor in breast cancer. Small vessels quantitatively assessed by staining with anti-CD31 antibodies correlate with lymph node involvement and are a better independent predictor of survival. There are many vascular growth factors, but predominant in primary tumors assessed by nuclease protection assays are vascular endothelial growth factor and platelet-derived endothelial cell growth factor. Acidic and basic fibroblast growth factor are also detectable. A common feature of these angiogenic factors is heparin binding, so novel analogues of suramin that can compete for heparin binding have been developed. These are more potent in vitro against endothelial cells and are less toxic in vivo, thereby giving a much better therapeutic ratio. Protein kinase C is also important in endothelial growth, as it is in carcinoma growth. Thus, a novel agent inhibiting this pathway, and inducing transforming growth factor-beta production has been assessed in a Phase I trial; this agent is bryostatin. It does not cause marrow suppression and has stimulatory effects of tumor necrosis factor-alpha and interleukin (IL)-6 production. High expression of epidermal growth factor (EGF) receptors and erbB-2 has been related to poor prognosis. EGF receptors are mainly regulated by transcription, as are some cases of high erbB-2 expression. Thus, a novel approach to gene therapy is being developed using direct tumor injection of cDNA, with a tumor specific promoter ligated to the IL-2 gene. This avoids many problems associated with targeting. Because IL-2 stimulation of cytotoxic T-cells will depend on appropriate antigen presentation, human lymphocyte antigen Class I expression was studied, as was the peptide transporter system RING4 (TAP1). Losses were found in 50% of cases, and in some cases only in lymph nodes but not primary cancers, thereby providing evidence for a role in suppressing metastasis. Thus, many new approaches to therapy are possible as a result of understanding growth factors and intracellular signaling pathways.
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PMID:Gene therapy through signal transduction pathways and angiogenic growth factors as therapeutic targets in breast cancer. 803 35

Tamoxifen has been an effective antiestrogen in suppressing breast cancer growth which is estrogen-responsive or dependent. Early studies have provided circumstantial evidence that transforming growth factor-beta (TGF-beta) may be an autocrine mediator of tamoxifen action. Therefore, it is both fundamentally important and clinically relevant to investigate the relationship between tamoxifen and TGF-beta. In this study, we demonstrated that CAMA-1 cells, which are sensitive to tamoxifen inhibition, did not respond to TGF-beta growth inhibition. The type I and II TGF-beta receptors were undetectable by the radio-ligand affinity labeling technique. Despite the presence of a normal TGF-beta type II receptor gene, the mRNA transcript of the gene was undetectable by the extremely sensitive Intron-differential RNA/PCR method. The possibility that the lack of TGF-beta receptors might be intimately linked to the absence of normal retinoblastoma (Rb) gene products, as suggested by previous studies of retinoblastoma cells, was further investigated. The lack of TGF-beta receptor expression was found due to reasons other than the absence, deletion or abnormality of the Rb gene because a normal Rb gene and its hyper- and hypo-phosphorylated protein products were detected in CAMA-1 cells. In conclusion, our results suggest that the TGF-beta system is not obligatory for antiestrogen growth inhibition of CAMA-1 cells.
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PMID:Absence of transforming growth factor-beta responsiveness in the tamoxifen growth-inhibited human breast cancer cell line CAMA-1. 820 Sep 13

The RRR-alpha-tocopheryl succinate form of vitamin E inhibits the proliferation of estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines in a dose-dependent manner in vitro. Analyses of cell-conditioned medium from RRR-alpha-tocopheryl succinate growth-inhibited cells revealed the presence of a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor-beta (TGF-beta) was established by 1) growth inhibition of the TGF-beta-responsive Mv1Lu-CCL-64 mink lung and murine CTLL-2 cell lines, 2) combination of physical characteristics including heat stability, acid stability, and Bio-Gel P-60 column chromatography elution profile, and 3) neutralization of the antiproliferative activity in the conditioned media by antibodies specific for TGF-beta.
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PMID:RRR-alpha-tocopheryl succinate inhibits proliferation and enhances secretion of transforming growth factor-beta (TGF-beta) by human breast cancer cells. 834 72

Gross cystic disease is a common benign breast disease that is associated with a twofold to fourfold increase in breast cancer risk. Both diseases are hormonally induced and may share a common biochemical environment conducive to abnormal proliferative responses. A large collection of breast cyst fluid samples was analyzed for growth factors associated with cell proliferation: epidermal growth factor (EGF), insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), platelet-derived growth factor (PDGF), transforming growth factor-alpha (TGF-alpha), and transforming growth factor-beta (TGF-beta). The data demonstrate that significant amounts of proliferative growth factors are present in breast cyst fluid of all cyst subtypes. The presence of IGF-II, PDGF, and TGF-beta in breast cyst fluid was confirmed for the first time. EGF, PDGF, and TGF-beta concentrations in breast cyst fluid were several times greater than reported for serum; IGF-I and IGF-II concentrations were several times lower. In the first 100 samples tested, no TGF-alpha was detected. Only EGF and IGF-II levels demonstrated a consistent correlation with apocrine type 1 cysts. These results demonstrated that effective concentrations of proliferative growth factors are in breast cyst fluid and suggest that adjacent breast tissue may be a probable source of synthesis. Growth factor profiles of breast cyst fluid may indicate the presence in breast tissue of a hormonal and proliferative environment permissive to subsequent cancer growth.
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PMID:Identification of multiple proliferative growth factors in breast cyst fluid. 836 33

Cancer chemoprevention is a new challenging issue for oncology. For breast cancer, different strategies for risk avoidance, chemopreventive measures and chemosuppressive interventions are being investigated. Attention is presently focused on two compounds, the synthetic retinoid fenretinide (4-HPR) and the antioestrogen tamoxifen, and their possible synergism. More data are now available on the expression and regulation of retinoic acid receptors in human breast cancer cells and on the consequences of the interaction of retinoids with plasma retinol binding protein. Mechanistic relationships between retinoids and growth factors like transforming growth factor-beta have been demonstrated in the frame of a central regulatory system of the state of differentiation and proliferation, in which tamoxifen is involved as well. Recent data from different trials using tamoxifen as adjuvant treatment have shown a decrease in the incidence of contralateral new primaries and that it could soon become unethical not to prescribe this drug to all node-negative oestrogen receptor-positive postmenopausal patients.
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PMID:Breast cancer chemoprevention. 838 73


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