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)

Predicting long-term outcome after breast-cancer diagnosis remains problematic, particularly for patients with clinically small, axillary lymph node- negative tumours. Evidence suggests that the lectin Helix pomatia agglutinin (HPA) identifies oligosaccharides associated with poor-prognosis cancer. Our aim was to identify oligosaccharides that bind HPA in aggressive breast cancers. Breast-cancer cell lines (MCF-7, BT-549 and BT-20) and a cell line from human milk (HBL-100), which showed a range of HPA-binding intensities, were used to extract HPA-binding glycoproteins. Oligosaccharides were released using anhydrous hydrazine and separated on a range of HPLC matrices. We investigated whether HPA-binding oligosaccharides from cell lines were present in human breast-cancer tissues, using 69 breast-cancer specimens from patients with between 5 and 10 years' follow-up. A monosialylated oligosaccharide was over-expressed in the cell line that bound HPA strongly. Further analysis by normal-phase HPLC showed that the 2-aminobenzamide-conjugated oligosaccharide had a hydrodynamic volume of 4.58 glucose units (HPAgly1). Increased expression of HPAgly1 was associated with HPA staining of breast-cancer specimens (Student's t-test p = 0.025). Analysis of oligosaccharide levels and disease-free survival after treatment for breast cancer indicated a shorter disease-free interval for patients with elevated levels of HPAgly1. This is the first time that histochemical lectin staining has been correlated with biochemical mapping of oligosaccharides. Using this approach, we have identified a monosialylated HPA lectin-binding oligosaccharide present in breast-cancer cells grown in vitro which is elevated in breast-cancer specimens that bind the lectin.
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PMID:Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer. 1124 16

Genistein is thought to contribute to the putative breast cancer preventive activity of soya. The mechanisms by which it arrests the growth of breast cells are incompletely understood. In order to explore generic features of the modulation of human breast cell growth by genistein, its effects on cell lines MCF-7, ZR-75.1, T47-D, MDA-MB 468, MDA-MB 231 and HBL 100 were compared. Genistein at 1 microM stimulated growth only in MCF-7 cells. At 10 microM it arrested the growth of all 6 cell types, however that of T47-D and HBL 100 cells only in medium with reduced (2%) fetal calf serum. Genistein induced apoptosis in only MDA-MB 468 cells. It arrested cells in the G2 stage of the cell cycle in all cell lines except ZR-75.1. Cells differed in their susceptibility towards inhibition by genistein of phorbol ester-induced proto-oncogene c-fos levels, transcription factor activator protein-1 (AP-1) activity and extracellular signal-regulated kinase (ERK) activity. Genistein augmented anisomycin-induced levels of proto-oncogene c-jun in ZR 75.1 and MCF-7 cells. The results suggest that induction of apoptosis, G2 cell cycle arrest and inhibition of c-fos expression, AP-1 transactivation and ERK phosphorylation may contribute to the growth-inhibitory effect of genistein in some breast cell types, but none of these effects of genistein constitutes a generic mode of growth-arresting action.
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PMID:Differences between human breast cell lines in susceptibility towards growth inhibition by genistein. 1150 5

Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer cells. However, exact regulatory mechanisms mediating and controlling this phenomenon are still unknown. In the present study, we have investigated the effect of anti-Her-2/neu antibody on apoptosis of HER-2/neu overexpressing human breast cancer cell lines SK-BR-3, HTB-24, HTB-25, HTB-27, HTB-128, HTB-130 and HTB-131 in relation to p53 genotype and bcl-2 status. SK-BR-3, HTB-24, HTB-128 and HTB-130 cells exhibited mutant p53, whereas wild type p53 was found in HTB-25, HTB-27 and HTB-131 cells. All seven cell lines weakly expressed bcl-2 protein (10-20%). Anti-Her-2/neu antibody, irrespective of p53 and bcl-2 status, induced apoptosis in all 7 cell lines dose- and time-dependently and correlated with Her-2/neu overexpression. In addition, incubation of cell lines with anti-Her-2/neu antibody did not alter p53 or bcl-2 expression. Anti-HER-2/neu antibody did not induce apoptosis in HER-2/neu negative HBL-100 and HTB-132 cell lines. Our results indicate that within the panel of tested breast cancer cell lines, anti-Her-2/neu antibody-induced apoptosis was independent from the presence of intact p53.
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PMID:Anti-Her-2/neu antibody induces apoptosis in Her-2/neu overexpressing breast cancer cells independently from p53 status. 1174

Ferritin is a ubiquitous iron storage protein existing in multiple isoforms composed of 24 heavy and light chain subunits. We describe here a third ferritin-related subunit cloned from human placenta cDNA library and named PLIF (placental immunomodulatory ferritin). The PLIF coding region is composed of ferritin heavy chain (FTH) sequence lacking the 65 C-terminal amino acids, which are substituted with a novel 48 amino acid domain (C48). In contrast to FTH, PLIF mRNA does not include the iron response element in the 5'-untranslated region, suggesting that PLIF synthesis is not regulated by iron. The linkage between the FTH and C48 domains created a restriction site for EcoRI. PLIF protein was found to localize in syncytiotrophoblasts of placentas (8 weeks of gestation) at the fetal-maternal interface. Increased levels of PLIF transcript and protein were also detected in the breast carcinoma cell lines T47D and MCF-7 but not in the benign corresponding cell line HBL-100. In vitro, PLIF was shown to down-modulate mixed lymphocyte reactions and to inhibit the proliferation of peripheral blood mononuclear cells stimulated with OKT3. The accumulated data indicate that PLIF is an embryonic immune factor involved in down-modulating the maternal immune recognition of the embryo toward anergy. This mechanism may have been adapted by breast cancer cells over expressing PLIF.
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PMID:PLIF, a novel human ferritin subunit from placenta with immunosuppressive activity. 1182 35

Kinetic studies of cell proliferation rates shed light on the growth dynamics of cancer. Most such studies are based on measurements of cell numbers that were evaluated in time intervals of about 12 h. Studies of the initial tumour growth with short measuring intervals are rare. This study was therefore designed with 1 h measuring intervals over a 24 h period. Human breast cancer cell lines (ZR-75-1, SK-BR-3, MCF-7) and a benign cell line (HBL-100) were used to study the hourly thymidine uptake as a measure of cells in synthesis. In parallel experiments, the same cell lines were also exposed to tumour necrosis factor alpha (TNF-alpha) to explore the effect of an apoptosis-inducing substance on initial tumour growth kinetics. In time-evolution plots, there was an oscillation of the labelling index of thymidine uptake for all investigated cell lines, with and without TNF-alpha. Based on the results obtained, a mathematical model was developed mimicking the real experiment. To describe the system dynamically a cellular automaton model was studied. The growth kinetics revealed by the simulation were in accordance with our experimental data. Two- and three-dimensional growth simulations of this computer model yielded objects morphologically similar to real images of human breast cancer. Almost identical fractal dimensions of the virtual and real tumours further supported this visual similarity. The cellular automata models could, therefore, be seen as a bridge towards realistic in vivo scenarios. From a clinical point of view, the results obtained may be applicable not only to primary tumours, but even to tumour cell microfoci and small metastases, which are a major concern in early metastasizing tumours such as breast cancer.
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PMID:Short-term rhythmic proliferation of human breast cancer cell lines: surface effects and fractal growth patterns. 1464 67

Autotaxin (ATX), originally isolated from human melanoma cells, is a novel metastasis-enhancing motogen and angiogenesis factor. In the present study, we compared the expression level of ATX mRNA between normal and breast cancer tissues and found that the expression of ATX mRNA was closely linked to invasiveness of cancer cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical analysis showed higher cellular ATX mRNA expression in the cancer than normal breast tissues. MDA-MB-435S breast cancer cells, expressing higher amount of ATX mRNA, showed greater relative invasiveness to fibroblast-conditioned medium (FCM) than MCF7, MDA-MB-231, and HBL-100 breast cancer cells. Furthermore, ATX-transfected MCF7 cells showed increased motility and invasiveness than vector-transfected MCF7 cells. Collectively, our results suggest that the expression of ATX is closely linked to the invasiveness of breast cancer cells.
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PMID:Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells. 1249 89

FosB is a member of the AP-1 family of transcription factors which represent important regulators of cell proliferation and differentiation. Based on prior results which indicated a role of FosB in breast cancer, we studied FosB protein and mRNA expression by immunohistochemistry and, partly, in situ hybridization in 68 mammary carcinomas and normal breast tissues. We found strong nuclear FosB immunoreactivity in epithelial cells of normal lobules and ducts, whereas carcinomas frequently showed loss of FosB expression (n = 8) or weak immunostaining (n = 24). Reduced FosB protein expression in tumors correlated with high grading (p = 0.005), negative estrogen and progesterone receptor status (p < 0.001), and strong HER2/neu expression (p = 0.025). Comparison with expression of seven cell-cycle regulators revealed an association of low/absent FosB staining with p16MTS1 overexpression (p = 0.005). RT-PCR showed expression of full-length FosB and the smaller splice variant FosB2 in most carcinomas and cell lines with and without FosB protein expression, indicating that both proteins are differentially regulated mainly at a post-transcriptional level. By sequence analysis of the coding region in four cell lines and 17 carcinomas we detected a mutation in HBL-100 cells. Our results indicate that high FosB expression might be necessary for normal proliferation and differentiation of mammary epithelial cells, and reduced FosB protein levels might be involved in dedifferentiation during breast tumorigenesis.
Breast Cancer Res Treat 2003 Feb
PMID:FosB is highly expressed in normal mammary epithelia, but down-regulated in poorly differentiated breast carcinomas. 1260 26

BRCA1 and BRCA2 breast cancer susceptibility genes are responsible for most of the hereditary breast cancers. Mutations in BRCA1 account for up to 40-50% of families with hereditary breast cancer only. Mutations in BRCA2 are linked to the other half of inherited breast cancer families and also to male breast cancer. On the contrary, no sporadic breast tumors have been shown to harbor mutations in BRCA1 and BRCA2 genes. It seems that altered expressions of BRCA1 and BRCA2 genes may contribute to breast cancer development. Moreover, BRCA1 and BRCA2 expressions are regulated in human breast cancer cell lines by estrogen. We addressed the issue of BRCA1 and BRCA2 expression in male breast cancers and gynecomastias. We investigated the presence of BRCA1 and BRCA2 proteins in male breast specimens by immunohistochemical analysis with a panel of antibodies elicited against BRCA1 and BRCA2. The specificity of each antibody has been verified by Western blotting in cell lines from different origins. The characterization of 6 anti-BRCA1 antibodies revealed a BRCA1 200-kDa protein detected in breast cell lines (MDA-MB 231, HBL 100, T-47D and MCF7) or in an acute leukemia (MOLT 4), known to overexpress BRCA1. All 5 anti-BRCA2 antibodies detected a BRCA2 384-kDa protein in the HBL100 and MCF7 breast cell lines. By immunohistochemistry, we found nuclear, perinuclear, endoplasmic reticulum, Golgi vesicle, secretion and apical cytoplasmic stainings in gynecomastias and sporadic and hereditary male breast cancers, for BRCA1 and BRCA2 protein expressions. We report an extensive expression of BRCA1 and BRCA2 proteins in different compartments of the mammary gland cells in male breast carcinomas and gynecomastias. This is consistent with the estrogen-dependent expression of BRCA1 and BRCA2 in human breast cells.
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PMID:Expression of BRCA1 and BRCA2 in male breast cancers and gynecomastias. 1268 Jan 64

The phytochemical resveratrol, found in grapes, berries and peanuts, has been found to possess cancer chemopreventive effects by inhibiting diverse cellular events associated with tumour initiation, promotion and progression. Resveratrol is also a phyto-oestrogen, binds to and activates oestrogen receptors that regulate the transcription of oestrogen-responsive target genes such as the breast cancer susceptibility genes BRCA1 and BRCA2. We investigated the effects of resveratrol on BRCA1 and BRCA2 expression in human breast cancer cell lines (MCF7, HBL 100 and MDA-MB 231) using quantitative real-time RT-PCR, and by perfusion chromatography of the proteins. All cell lines were treated with 30 microM resveratrol. The expressions of BRCA1 and BRCA2 mRNAs were increased although no change in the expression of the proteins were found. These data indicate that resveratrol at 30 micro M can increase expression of genes involved in the aggressiveness of human breast tumour cell lines.
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PMID:Resveratrol increases BRCA1 and BRCA2 mRNA expression in breast tumour cell lines. 1283 19

The purpose of this study was to demonstrate the effects of lycopene, the major tomato carotenoid, on the expression of the BRCA1 and BRCA2 genes in three breast tumour cell lines, MCF-7, HBL-100, MDA-MB-231 and the fibrocystic breast cell line MCF-10a. Flow cytometry analysis showed a G(1)/S phase cell cycle-arrest after treatment of the cells with 10 microM lycopene for 48 h. mRNA expression was studied by quantitative reverse transcription-polymerase chain reaction using the Taqman method. We observed an increase of BRCA1 and BRCA2 mRNA in the oestrogen receptor (ER)-positive cell lines (MCF-7 and HBL-100), and a decrease (MDA-MB-231) or no change (MCF-10a) in the ER-negative cell lines. BRCA1 and BRCA2 proteins were quantified by perfusion affinity chromatography. No variation in their expression was observed. These preliminary results on the effects of lycopene on the expression of BRCA1 and BRCA2 oncosuppressor genes in breast cancer may reflect cross-talk between the oestrogen and retinoic acid receptor (RAR) pathways.
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PMID:The effects of lycopene on the proliferation of human breast cells and BRCA1 and BRCA2 gene expression. 1525 Nov 68


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