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

The effect of a number of steroids, growth factors, and peptides on aromatase activity in two estrogen receptor positive breast cancer cell lines (MCF7 and T47D) was investigated. The cells were incubated in Dulbecco's minimum essential medium containing phenol red and 10% fetal calf serum. Pronounced differences in basal aromatase activity and different responses to the addition of experimental agents were found in the two cell lines. Aromatase activity in MCF7 cells was significantly stimulated by phorbol 12,13-diacetate [PDA], dibutyryl cyclic AMP [(Bu)2cAMP], transforming growth factor alpha, and epidermal growth factor individually and PDA and (Bu)2cAMP in combination, while it was inhibited by dexamethasone and unaffected by transforming growth factor beta, fibroblast growth factor, platelet-derived growth factor, prolactin, and tamoxifen. Addition of cortisol to MCF7 cells had no effect on aromatase activity at 1 nM, caused suppression of activity at 10 nM and stimulated activity at 100 nM. Aromatase activity in T47D cells was stimulated by transforming growth factor alpha, epidermal growth factor, platelet-derived growth factor, prolactin, dexamethasone, and cortisol individually and PDA and (Bu)2cAMP in combination. It was unaffected by transforming growth factor beta, PDA, (Bu)2cAMP, and fibroblast growth factor. These findings suggest that aromatase activity is induced by agents which stimulate cyclic AMP-dependent protein kinases [e.g., (Bu)2cAMP] and that this effect is potentiated by factors which stimulate protein kinase C [e.g., PDA]. The effect on aromatase activity of growth factors, the actions of which are believed to be mediated by receptors linked to tyrosine kinase activity, is not as clearly defined, with a factor causing stimulation, inhibition, and no change in activity depending on the tissue concerned. Further insight into these differences will require resolution of the molecular mechanisms that mediate the actions of stimulatory and repressive growth factors on aromatase activity of oestrogen-producing cells.
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PMID:Steroid and growth factor modulation of aromatase activity in MCF7 and T47D breast carcinoma cell lines. 131 30

Plasma levels of platelet-derived growth factor (PDGF) were measured in 58 female patients with breast cancer and in 9 normal female control subjects by means of a specific radioimmunoassay. Levels in normal control subjects were all below the lower limits of detection by the assay (1.56 fmol/100 microliters plasma). Two of 17 (12%) patients with stage 2 breast cancer had detectable plasma levels. Among patients with Stage 4 breast cancer 13/41 (32%) had significantly elevated levels (greater than 2 times the lower limit of sensitivity of the assay). Patients with elevated PDGF levels had a significantly greater degree of metastatic involvement and significantly shorter survival. Apart from being a marker of aggressive high bulk breast cancer, PDGF may be involved in the acceleration of growth of some metastatic breast tumors.
Breast Cancer Res Treat 1991 Dec
PMID:Platelet-derived growth factor (PDGF) in plasma of breast cancer patients: correlation with stage and rate of progression. 166 86

Various investigators have shown that the IGFs are mitogens for breast cancer cells. The expression of the IGF receptors is seen in most breast cancer cell lines and tissues, suggesting that most breast cancers have the ability to respond to the IGFs. Although authentic IGF-I is not expressed by breast cancer cell lines, it is possible that an IGF-related peptide that can be detected immunologically is expressed. Furthermore, in estrogen responsive xenotransplants, changes in the level of IGF-II mRNA correlate directly with estrogen-mediated changes in tumor growth. These observations suggest that IGF-II may be important in tumorigenesis and may serve as an autocrine growth stimulator of breast cancer cells. When human breast cancer tissues are studied, IGF-I and IGF-II mRNA expression are commonly seen. However, in situ hybridization studies suggest that IGF-I mRNA is expressed mainly by the stromal elements, while IGF-II mRNA can be found both in stroma and malignant epithelial cells. These observations support the studies done with breast cancer cell lines; IGF-I may stimulate cells via a paracrine pathway, while IGF-II may act as both an autocrine and paracrine growth factor. In addition, IGF-BPs are commonly expressed by breast cancer cells in culture, and it is possible that expression of the IGF-BPs act to modulate the effects of either IGF-I or IGF-II. We propose that the IGFs are important stimulators of breast cancer cells and that their growth promoting effects may be mediated by autocrine, paracrine, or endocrine mechanisms. Furthermore, interactions between the stroma and malignant epithelial cells may be important in regulating the growth of breast cancer. The biological importance of a fibroblast-epithelial cell interaction has been demonstrated in a normal mouse mammary cell line; morphological and functional changes in epithelial cells were induced when the cells were in direct contact with fibroblasts. Similar mechanisms may be important in malignant breast epithelial cells. For example, many breast cancer cells produce platelet-derived growth factor (PDGF) yet have no PDGF receptor. PDGF has been demonstrated to increase IGF-I production by fibroblasts, and a dual paracrine pathway involving PDGF and IGF-I expression by epithelial cells and stromal cells could be envisioned. The pathways through which the IGF system may function in human breast cancer are schematically represented in figure 1. Further work in our laboratory is directed at clarifying the role for the IGFs in breast cancer growth.
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PMID:The insulin-like growth factors, their receptors, and their binding proteins in human breast cancer. 167 92

The neu proto-oncogene product has been found to exist in two interconvertible forms in G8/DHFR mouse fibroblasts. The 185-kilodalton form (p185) present in growing cells is replaced by a 175-kilodalton form (p175) under conditions of serum starvation. This low molecular weight form accounts almost exclusively for the phosphotyrosine content of the receptor and is associated with increased tyrosine kinase activity. Addition of serum, platelet-derived growth factor or tumor promoter induces conversion of p175 to p185 within minutes, and this increase in molecular weight is associated with phosphorylation of serine and threonine; removal of serum growth factors is followed by replacement of p185 with p175 over several hours. Unlike G8/DHFR cells, the human breast cancer cell line SK-Br-3 expresses a high molecular weight neu/HER2 receptor with unchanged phosphotyrosine content in both serum-starved and serum-stimulated cultures. These findings indicate that activation of the neu proto-oncogene product in G8/DHFR cells may be regulated in part by protein kinase C-mediated receptor transmodulation rather than by ligand availability alone.
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PMID:Modulation of a Mr 175,000 c-neu receptor isoform in G8/DHFR cells by serum starvation. 197 80

In milk from substrains of mice with varying incidences of developing mammary tumor, we have isolated a specific mitogenic activity, which is unique in that it identifies mice with mammary tumor and predicts those mice that will eventually develop mammary tumor. None of the milk samples from control mice, who never developed mammary tumor, contained this specific predictive mitogenic activity. Chemical characterization has shown this specific mitogenic activity to be acid- and heat-stable and resistant to reducing agents. Partial purification, by ion-exchange, high-performance liquid chromatography size-exclusion, and isoelectrofocusing techniques, of this specific mitogenic activity from milk of mice that had or eventually developed mammary tumor identifies several peptide growth factor components in a 6-10 kDa molecular weight range. Of known growth factors, radioassay techniques identify an insulin-like growth factor-1-like peptide as a major component. Small amounts of platelet-derived growth factor and transforming growth factor-beta activities also were present. Our results suggest that a subset of growth factors that are diagnostic of the presence of murine mammary tumor and predictive of eventual tumor development may be early indicators of the transition of a competent cell to a progressively malignant state. Similar studies of a secreted body fluid from women at risk for breast cancer may lead to the identification of a specific biologic tumor marker for breast cancer.
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PMID:Specific growth factor activity identifies and predicts murine mammary tumor. 198 33

P19 EPI-7, a differentiated murine embryonal carcinoma cell line with an epithelioid morphology, does not require external growth factors for proliferation under clonal and subconfluent conditions. At saturation density, however, cells become quiescent in the G1/G0 phase of the cell cycle from which they can be restimulated, particularly upon addition of epidermal growth factor. Medium conditioned by confluent P19 EPI-7 cultures is able to enhance clonal outgrowth of this cell line, suggesting that autocrine growth factor loops may be acting in these cells. Analysis of conditioned serum-free medium shows that this cell line produces a platelet-derived growth factor-like growth factor, next to a type beta transforming growth factor and large amounts of insulin-like growth factor II (IGF-II) and an IGF-binding protein with high specificity for IGF-II. This latter observation has been confirmed by the use of a specific bioassay for IGFs, based on their ability to specifically stimulate proliferation of MCF-7 human breast cancer cells. The amount of IGF-II produced (0.5 mg/liter conditioned medium) makes P19 EPI-7 one of the best producing cell lines for this factor described so far. Receptor cross-linking analysis shows that this cell line contains IGF-I receptors, but no specific receptors for IGF-II. Depending on the conditions tested, transforming growth factor-beta 1 either act as a growth-stimulating factor or as a strong growth inhibitory factor. These data demonstrate that upon cellular differentiation, embryonal carcinoma cells can be formed which produce polypeptide growth factors and are also able to respond to such factors. These observations are discussed in the light of the role of autocrine and paracrine growth stimulation processes during early murine development.
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PMID:Production of insulin-like growth factors, platelet-derived growth factor, and transforming growth factors and their role in the density-dependent growth regulation of a differentiated embryonal carcinoma cell line. 253 20

Human platelet lysates contained potent mitogenic activities for MCF-7 human breast-cancer cells in serum-free-defined media. Because these activities were not replaced by known platelet mitogens, such as platelet-derived growth factor or transforming growth factor beta, we sought to identify the breast cancer cell mitogens by purification and N alpha amino-acid sequencing. Acetic acid extracts of outdated human platelets were concentrated by ammonium sulfate precipitation and fractionated on Sephadex G-50 and Bio-Gel P-10 columns in 0.5 mol/L acetic acid. Two major activities were resolved by molecular sieve methods and fractionated further by reverse-phase high-performance liquid chromatography (HPLC). Purifications (70,000 to 870,000-fold) were accomplished yielding mol wt 7,400 products that were homogeneous as determined by iodination, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and autoradiography. The factors were identified as insulinlike growth factor I (IGF-I) and II (IGF-II) and truncated IGF-I by N alpha amino acid microsequencing. In dose-response experiments, platelet-derived IGF-I and IGF-II promoted multiple divisions of the MCF-7 cells with ED50 values of 12 and 100 pg/mL, respectively. The specific activities and other bioassay characteristics of platelet-derived IGF-I and IGF-II were similar to those of recombinant-produced human growth factors. This is the first report of the purification of insulinlike growth factors from human platelet lysates.
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PMID:Human platelet-derived mitogens. I. Identification of insulinlike growth factors I and II by purification and N alpha amino acid sequence analysis. 275 53

The breast cancer cell line T47D produces factors which show mitogenic activity for 3T3 cells. Here we describe the partial purification of one of these factors and show that it has properties similar to platelet-derived growth factor (PDGF). The T47D factor is a heat-stable hydrophobic protein with a molecular weight of around 30,000, which inhibits the binding of 125I-EGF in a temperature-dependent manner. This 30 kd protein does not act synergistically with PDGF or fibroblast-derived growth factor (FDGF; also PDGF-like) in stimulating DNA synthesis; moreover, like these two factors, its mitogenic activity can be inhibited by an antiserum raised against human PDGF. A PDGF-like growth factor was also found in the serum-free medium of the breast cancer cell line MDA-MB-157. Since PDGF acts on mesenchymal cells, the production of PDGF-like growth factors by breast cancer cells suggests a basis for the intense stromal reaction seen in human breast cancers.
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PMID:Production of PDGF-like growth factor by breast cancer cell lines. 299 Nov 48

We report that human breast cancer cells secrete a growth factor that is biologically and immunologically similar to platelet-derived growth factor (PDGF). Serum-free medium conditioned by estrogen-independent MDA-MB-231 or estrogen-dependent MCF-7 cells contains a mitogenic or "competence" activity that is capable of inducing incorporation of [3H]thymidine into quiescent Swiss 3T3 cells in the presence of platelet-poor plasma. In addition, the conditioned medium contains an activity that competes with 125I-labeled PDGF for binding to PDGF receptors on normal human fibroblasts. The secretion of PDGF-like activity by the hormone-responsive cell line MCF-7 is stimulated by 17 beta-estradiol. Like authentic PDGF, the PDGF-like activity produced by breast cancer cells is stable after acid and heat treatment (95 degrees C) and inhibited by reducing agents. The mitogenic activity comigrates with a material of approximately equal to 30 kDa on NaDodSO4/polyacrylamide gels. Immunoprecipitation with PDGF antiserum of proteins from metabolically labeled cell lysates and conditioned medium followed by analysis on nonreducing NaDodSO4/polyacrylamide gels identified proteins of 30 and 34 kDa. Upon reduction, the 30- and 34-kDa bands were converted to 15- and 16-kDa bands suggesting that the immunoprecipitated proteins were made up of two disulfide-linked polypeptides similar to PDGF. Hybridization studies with cDNA probes for the A chain of PDGF and the B chain of PDGF/SIS identified transcripts for both PDGF chains in the MCF-7 and MDA-MB-231 cells. The data summarized above provide conclusive evidence for the synthesis and hormonally regulated secretion of a PDGF-like mitogen by breast carcinoma cells. Production of a PDGF-like growth factor by breast cancer cell lines may be important in mediating paracrine stimulation of tumor growth.
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PMID:Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines. 303 6

MCF-7 human breast cancer cells have been studied for hormonal regulation of secretion of an insulin growth factor-I (IGF-I)-related growth factor. 17 beta-Estradiol, which is required for tumorigenesis of the cell line in the nude mouse and which stimulates proliferation in vitro, was able to significantly induce IGF-I secretion at 10(-13) M, with maximal induction at 10(-11) M. Under optimal conditions IGF-I could be induced 4-fold after 4 days. Demonstration of estrogenic stimulations required removal of phenol red, a weak estrogen, from the cell culture medium. In addition to estrogen, insulin, epidermal growth factor, and transforming growth factor alpha induce both cellular proliferation and IGF-I secretion, while growth inhibitory antiestrogens, transforming growth factor beta, and glucocorticoids have the opposite effect. In each case, modulations in IGF-I secretion preceeded effects on cellular proliferation. IGF-I was not regulated by human GH, basic fibroblast growth factor, platelet-derived growth factor, or PRL, none of which affected proliferation rate. Thus, regulation of IGF-I secretion in human breast cancer is controlled by different hormones from those previously reported in human fibroblasts. Regulation of IGF-I by neither estrogen nor antiestrogen was associated with changes in steady-state mRNA levels; thus regulation may occur at a step beyond mRNA. We conclude that IGF-I production is tightly coupled to growth regulation by estrogens, antiestrogens, and other hormones and may contribute to autocrine and/or paracrine growth regulation by these agents in breast cancer.
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PMID:Multihormonal regulation of insulin-like growth factor-I-related protein in MCF-7 human breast cancer cells. 304 Dec 62


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