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

Two human breast cancer cell lines (MCF-7 and MDA-MB-231) and one cell line derived from normal human breast (HBL-100) were examined for the presence of aromatase activity by determining the amounts of [3H]estradiol ([3H]E2) formed by cell cultures incubated with [3H]testosterone. Aromatase activity was demonstrable in both breast cancer cell lines, but estradiol synthesis was not observed in HBL-100 cultures. The [3H]E2 content of MCF-7 cultures rose as a function of incubation time and substrate concentration. Furthermore, [3H]E2 formation by this cell line was suppressed by several known inhibitors of human placental aromatase. These observations represent the first evidence that some lines of continuously cultured human breast cancer cells, like some human breast tumors, are capable of forming estrogen from an extracellular precursor steroid. Cultured breast cells may provide model systems for investigating the relative importance of intracellular estrogen formation in the regulation of human breast cancer cell growth.
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PMID:Estradiol formation from testosterone by continuously cultured human breast cancer cells. 45 46

Distinct proteins complexed with somatostatin and the somatostatin analogue BIM-23014C were revealed in human breast cancer cells using the cross-linking assay. One BIM-23014C-specific complex (Mr 57,000) was observed in MCF-7 (monolayer, nodule, and tumor) and T47D. Growth inhibition of MCF-7 tumor xenografts by BIM-23014C was dose related in the 6-day subrenal capsule assay. Three complexes (Mr 27,000, 42,000, and 57,000) were detected in MDA-MB-231, and no complex was visible in HBL-100. No correlation was found between receptors for BIM-23014C and epidermal growth factor in these lines. Twenty-seven of 30 human breast tumors (90%) had at least one BIM-23014C receptor. Sixteen had three complexes (Mr 27,000, 42,000, and 57,000). Six had the two complexes (Mr 27,000 and 57,000), two had Mr 42,000 and 57,000 complexes, two had just the Mr 27,000 complex, and one had just the Mr 42,000 complex. The presence of the three BIM-23014C receptors was positively correlated (P less than 0.05) to the low amount of sex steroid receptors (less than 20 fmol/mg) [seven of eight (estrogen receptor negative, progesterone receptor negative) versus four of 14 (estrogen receptor positive, progesterone receptor positive)]. Another positive correlation was established between the absence of progesterone receptors and the presence of these three complexes [12 of 16 (progesterone receptor negative) versus four of 14 (progesterone receptor positive)]. This high percentage of BIM-23014C receptor-positive biopsies and its inhibitory activity would support its clinical potential for the treatment of breast cancer.
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PMID:Molecular heterogeneity of somatostatin analogue BIM-23014C receptors in human breast carcinoma cells using the chemical cross-linking assay. 134 85

Estrogen receptor (ER) binding has been shown to decrease in breast cancer cell lines exposed to sodium butyrate; however, the underlying mechanisms are unknown. In MCF-7 breast cancer cells, butyrate caused a rapid time- and concentration-dependent decrease in ER mRNA levels, apparent by 3 h at 3 mM butyrate. ER gene transcription rate was decreased and cycloheximide co-treatment did not relieve this inhibitory effect, suggesting that the butyrate effect was not dependent on ongoing protein synthesis. In both MCF-7 and T-47D cells the decrease in ER mRNA was mirrored by an increase in the level of epidermal growth factor receptor (EGF-R) mRNA. A marked inverse relationship exists between ER and EGF-R in human breast cancer biopsies and cell lines, and the reciprocal modulation of these genes by butyrate suggests that the expression of ER and EGF-R may be co-regulated. This relationship was further investigated in lines expressing only one or the other receptor. In the ER-positive EGF-R-negative line, MDA-MB-134-VI, butyrate exposure decreased ER mRNA levels, implying that the regulation of ER mRNA by butyrate is independent of EGF-R expression. However, butyrate decreased EGF-R mRNA in two ER-negative lines, MDA-MB-231 and HBL-100. As this effect differed from that in ER-positive lines, the regulation of EGF-R may depend on the expression of ER. The possibility that ER and EGF-R gene expression are closely linked has implications in the understanding of progression of human breast cancers to a hormone-independent phenotype and for the use of ER and EGF-R levels as independent prognostic indicators.
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PMID:Effect of sodium butyrate on estrogen receptor and epidermal growth factor receptor gene expression in human breast cancer cell lines. 151 34

The expression of the 17 beta-hydroxysteroid dehydrogenase (17-HSD) gene in a series of human breast cancer cell lines was studied by Northern blot hybridization with a cDNA probe and by a time-resolved immunofluorometric assay using polyclonal antibodies against the enzyme protein. The 17-HSD enzyme protein concentration was measured in the 800 x g cell extract. A high concentration was measured in the BT-20 cell line, corresponding to one-fourth of the average concentration in placental tissue. Western blot analysis indicated that the antigen corresponded to a single Mr 35,000 band. In 2 other cell lines (MDA-MB-361 and T-47D), the 17-HSD protein concentration was much lower, but still measurable, whereas in the remaining 5 cell lines (HBL-100, MCF-7, MDA-MB-231, MDA-MB-468, and ZR-75-1) it was below the detection limit of the assay. Treatment of the cells for 5 days with the synthetic progestin, ORG2058, resulted in an increase of the 17-HSD protein concentration only in the T-47D cell line. By Northern blot analysis, a low level of 2.3-kilobase mRNA transcripts was detected in all 8 cell lines. In addition, a 1.3-kilobase 17-HSD mRNA was present in the samples from the 3 cell lines containing measurable amounts of 17-HSD protein in the cell extract, and the band intensities were proportional to the amount of protein measured with the immunofluorometric assay. Only in the T-47D cell line did progestin treatment correspond to an increased amount of the 17-HSD 1.3-kilobase mRNA. These results suggest that the 1.3-kilobase mRNA for 17-HSD is the form most closely associated with protein expression and is also the only form responding to the progestin induction of the 17-HSD gene.
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PMID:17 beta-hydroxysteroid dehydrogenase gene expression in human breast cancer cells: regulation of expression by a progestin. 172 3

A mammary-derived growth factor, MDGF1, which stimulates collagen synthesis and proliferation in mammary epithelial cells was previously detected and purified from human milk and primary human breast tumors. MDGF1 binds to putative cell-surface receptors of 120-140 kDa and stimulates proliferation of normal and malignant human mammary epithelial cells. Partial protein sequence (N-terminal 18 amino acid sequence) shows that MDGF1 has no homology to any other known growth-promoting peptides. Polyclonal antiserum raised against this synthetic peptide recognizes native milk-derived MDGF1. We hypothesize that MDGF1 might be an autocrine or paracrine factor produced by and acting on normal and malignant human breast epithelial cells possessing MDGF1 receptors. As a first step in testing this possibility, we examined whether human breast epithelial cells in culture produce the growth factor. A protein with the size of MDGF1 was immunologically detected in the concentrated conditioned medium prepared from human breast cancer cell line MDA-MB 231, the mammary-derived but nontumorigenic HBL-100 line, and the normal reduction mammoplasty-derived, nonimmortalized 184 cell strain. A competitive radioreceptor assay (RRA) was used to estimate the level of MDGF1 in the conditioned medium. MDGF1 was present in the nanogram range per 1 million cells. A 62-kDa protein was detected in the above cell lysates by Western immunoblotting or by immunoprecipitation of metabolically labeled cell-conditioned media. The polyclonal antisera directed against the 18 amino acid peptide sequence from milk-derived MDGF1 could adsorb MDGF1 biological activity from conditioned medium. In vitro translation of cell mRNA yielded a protein of 55 kDa which was immunoprecipitated by anti-MDGF1 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Production and characterization of mammary-derived growth factor 1 in mammary epithelial cell lines. 173 16

We studied the mode of iron transport and storage in a human breast cancer cell line (HT-24) in comparison with a breast epithelial cell line (HBL-100). It was found that HT-24 cells incorporated over 18 h more 59Fe as compared to HBL-100 (24 vs. 16%). Yet, the number of surface transferrin-binding sites was less in cancer cells (6.2 x 10(5)) than in epithelial cells (8 x 10(5)). Moreover, the transferrin receptors in cancer cells were less affected by iron overloading as compared with epithelial cells. Following immunoprecipitation of isoferritins with specific monoclonal antibodies (MoAbs), it was found that the quantity of de novo synthesized normal ferritin immunoprecipitated with CM-G-8 MoAb was similar in both cancer and epithelial cells. However, the amount of 59Fe incorporated into the protein was significantly higher in HBL-100 cells. In contrast, HT-24 cells synthesized a high amount of placental-like isoferritin (PLF) immunoprecipitated with CM-H-9 MoAb which was significantly higher (p less than 0.001) than in epithelial cells. This isoferritin was characterized by its low iron incorporation. It is noteworthy that the ratio of PLF to normal ferritin was 2:1 in cancer cells and 0.7:1 in epithelial cells, indicating that PLF is a major type of isoferritin synthesized by HT-24 breast cancer cells. Furthermore, a significant amount of PLF was expressed on the surface of cancer cells as compared to epithelial cells. The results of this study suggest that iron supply and distribution in breast neoplastic cells are not controlled similarly to normal cells.
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PMID:Comparison of transferrin receptors, iron content and isoferritin profile in normal and malignant human breast cell lines. 204 66

The mouse monoclonal antibody MA5, generated versus a membrane-enriched extract of breast cancer metastatic to liver, detects one or two high molecular weight species (greater than 200 kD) in breast tumor membranes, human milk fat globule membranes, and various breast tumor cell lines. From comparative studies of five breast carcinoma lines (BT20, BT549, MCF-7, T47D, and ZR75-1), as well as an epithelial line established from milk (HBL-100), we report the stimulation of expression of MA5-reactive antigen in a mucinous breast tumor cell line (BT549) through the use of a culture medium supplemented with charcoal-absorbed fetal calf serum, insulin, and hydrocortisone. Large amounts of aggregated MA5-reactive antigen are secreted into the culture medium and can be recovered from the media for further purification by centrifugation. These findings suggest that BT549 cells, grown in the special nutritive medium, may be useful in providing an ample source of epithelial membrane antigen (also termed polymorphic epithelial mucin) for standardization of clinical assay protocols, as well as provide a model system for studies of the regulation of expression for this class of antigens in breast carcinoma.
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PMID:Enhanced expression and secretion of an epithelial membrane antigen (MA5) in a human mucinous breast tumor line (BT549). 216 Jul 22

A mammalian cell expression plasmid, pH beta-Aro, containing the human placenta aromatase complementary DNA was constructed. The prepared plasmid was used to transfect breast cancer cells (MCF-7), noncancerous breast cells (HBL-100), and Chinese hamster ovary cells by a stable expression method. While the maximum velocities for aromatase expressed in three types of cells were different (10-201 pmol of [3H2O] formed/h/mg) using [1 beta, 2 beta-3H]androst-4-ene-3,17-dione as the substrate, the apparent Michaelis-Menten constants were found to be similar (39.9-57.8 nM) and were within the range determined for the enzyme existing in human placenta. The expressed activities were inhibited by the known aromatase inhibitors, 4-hydroxyandrostenedione and aminoglutethimide, at concentrations that normally inhibit the human placental aromatase. However, it was found that the inhibition profiles were different for aromatase expressed in different types of cells, suggesting that other factors, such as the uptake of the inhibitor, may also play a role in determining the inhibition efficiency. These constructed aromatase expressing mammalian cell lines will be very useful tools for aromatase inhibitor screening.
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PMID:Stable expression of human aromatase complementary DNA in mammalian cells: a useful system for aromatase inhibitor screening. 220 60

A complementary DNA library has been constructed from the polyadenylated mRNA of steroid-deprived T-47D cells which had been restimulated with estrogen for 24 h. Screening of 15,000 recombinants by sequential rounds of colony, Southern and Northern blot differential hybridization has identified eight different clones which vary in abundance and are stimulated between 2.5- and 8-fold by estrogen. Whereas five recombinants hybridize to single mRNA sequences, two clones, pSyd 2 and pSyd 8, appear to hybridize weakly to an addition mRNA sequence and one clone, pSyd 3, hybridizes to a multiple mRNA species (1.9, 1.7, 0.9, and 0.5 kilobases). Furthermore, at least one clone, pSyd 2, appears to be expressed only in ER-positive cells. While its level of expression is stimulated by estrogen approximately 4-fold in all the estrogen and progesterone receptor-positive cell lines tested (T-47D, ZR-75-1, and MCF-7), pSyd 2 levels in the estrogen and progesterone receptor-negative HBL-100 cell line were lower than the corresponding levels in estrogen-stimulated T-47D cells and were unresponsive to estradiol. These results show that we have isolated several estrogen-responsive sequences which will be useful in studying hormone regulation of gene expression and may provide additional markers of hormone responsiveness in breast cancer.
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PMID:Cloning of estrogen-responsive messenger RNAs in the T-47D human breast cancer cell line. 235 59

A previous study from this laboratory (Koga et al., Cancer Res., 48: 2734-2739, 1988) demonstrated that the growth inhibitory effect of 1,25-dihydroxyvitamin D3 in human breast cancer cells in vitro was associated with a decline in the concentration of epidermal growth factor receptor (EGF-R). In the present study experiments were undertaken with the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), an agent known to decrease EGF-R binding, in order to further define the relationship between changes in EGF-R binding and changes in growth rates in 10 human breast cancer cell lines. Treatment with TPA decreased the rate of cell proliferation in all cell lines except BT 474 in which a slight increase in proliferation rate was observed. Sensitivity to TPA was unrelated to estrogen receptor (ER) status and a wide spectrum of sensitivities was apparent. The concentrations of TPA that produced a 25% decrease in cell number ranged from less than 0.25 nM for MCF 7M and BT 20 cells to greater than 10 nM for the HBL 100, T 47D, and ZR 75-1 cell lines. Growth inhibition was associated with a block in cell cycle progression in the G1 and G2 + M phases of the cell cycle. In all cell lines studied, except BT 474, TPA treatment resulted in a reduction in the ability of cells to bind EGF. Saturation analysis revealed marked differences between the effects of TPA on EGF binding in ER+ and ER- cell lines. In ER+ cell lines, 2-h treatment with 10 nM TPA resulted in a marked reduction in the number of high affinity EGF-R sites and a significant decrease in binding affinity. Among this group of cell lines there was a significant positive correlation between the ability of TPA to decrease cell growth and the TPA-induced decrease in the number of EGF-R sites/cell (r = 0.82, P less than 0.03). In ER- cell lines, TPA-induced growth inhibition and the minor changes in EGF-R concentration were unrelated. However, growth inhibition was negatively correlated with TPA-induced changes in apparent affinity of the EGF-R (r = 1.00, P less than 0.003) and in the same rank order as the EGF-R concentration in control cells. These data demonstrate differential relationships between TPA-induced changes in growth and EGF-R binding in ER+ and ER- breast cancer cells, thus supporting the view that growth regulatory pathways are markedly different in these two subtypes of human breast cancer.
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PMID:Differential effects of phorbol ester on epidermal growth factor receptors in estrogen receptor-positive and -negative breast cancer cell lines. 237 49


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