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

MDA-MB-231 (MDA-231) human breast cancer cells have a high proliferation rate, lack the estrogen receptor, express the intermediate filament vimentin, the hyaluronan receptor CD44, and are able to form tumors in nude mice. The MDA-231 cell line has been used in our laboratory to examine the role of the peripheral-type benzodiazepine receptor (PBR) in the progression of cancer. During these studies 2 populations of MDA-231 cells were subcloned based on the levels of PBR. The subclones proliferated at approximately the same rate, lacked the estrogen receptor, expressed vimentin and CD44, and had the same in vitro chemoinvasive and chemotactic potential. Both restriction fragment length polymorphism and comparative genomic hybridization analyses of genomic DNA from these cells indicated that both subclones are of the same genetic lineage. Only the subclone with high PBR levels, however, was able to form tumors when injected in SCID mice. These data suggest that the ability of MDA-231 cells to form tumors in vivo may depend on the amount of PBR present in the cells.
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PMID:Peripheral-type benzodiazepine receptor levels correlate with the ability of human breast cancer MDA-MB-231 cell line to grow in SCID mice. 1174 9

Glycogen-rich, clear cell carcinoma of the breast (GCC) is a rare type of breast cancer. Histological features are usually those of ductal carcinoma, but cases featuring lobular, tubular, and mixed ductal-tubular carcinoma have been reported. The presence of "numerous cells with clear cytoplasm" has been reported in some cases of primary neuro-endocrine tumors of the breast. Moreover, no case of GCC of the breast with neuro-endocrine features has been described. We report a case of 33-year-old woman with a palpable lump of the right breast. Fresh tissue obtained from the operating theatre was fixed in 10% formalin and routinely processed to paraffin. Serial sections were stained with haematoxylin and eosin (H&E), periodic acid Schiff (PAS) and PAS following diastase digestion (PASd); other sections were processed for immunohistological detection of chromogranin, synaptophysin, vimentin and smooth muscle actin. For electron microscopy, the tissue was fixed in 2.5% glutaraldehyde in cacodylate buffer. The samples were post-fixed in osmium, dehydrated in ethanol and embedded in araldite. Thin sections, counterstained in uranyl acetate and lead citrate, were studied under a Philips 400T electron microscope. The lump at histological examination was entirely composed of optically clear, neoplastic cells. The cytoplasm was filled with numerous PAS-positive granules which did not stain after the diastase digestion, leading to a diagnosis of GCC of the breast. Some histological (i.e. pattern of growth, blunt edges of neoplastic glands and numerous vessels) and cytological features (i.e. nuclear monomorphism and fine chromatin) prompted us to investigate the possible neuro-endocrine differentiation of the lesion. Immunohistochemical and ultrastructural studies strongly support such hypothesis. To the best of our knowledge, we report the first case of GCC of the breast with neuro-endocrine features.
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PMID:[Glycogen-rich clear-cell breast carcinoma with neuroendocrine differentiation features]. 1178 21

A 36-year-old woman presented with a 10 mm diameter mass in the right breast. Since the mass persisted for 3 months after detection and mammary carcinoma was suspected based on ultrasonographic findings, the mass was resected. Histologically, the mass demonstrated proliferative margins and consisted of spindle cells with bland cytologic features and abundant collagen. Immunohistochemically, the spindle cells were positive for vimentin and smooth muscle actin, and were negative for cytokeratins and desmin. Furthermore, the cells showed MIB-1 immunoreactivity with a MIB-1 labeling index of 4.1. Based on these findings, was diagnosed fibromatosis. Breast fibromatosis is rare and is usually misdiagnosed as breast carcinoma preoperatively. To date, only 10 cases of breast fibromatosis have been reported in Japan. Among the reported cases in Japan, our patient presented with the smallest mass, and ultrasonographic findings in this case were the same as those of other cases. Our experience and a review of the literature indicated that differentiation of fibromatosis from carcinoma is very difficult by ultrasonographic examination. In our case, despite involvement of the surgical margins, there was no recurrence. This may be attributed to the small size of the mass and focal exposure.
Breast Cancer 2002
PMID:A case of fibromatosis of the breast. 1201 99

Cell lines are traditionally used as tools for in vitro studies of breast cancer. It is highly debatable however, because of the genetic drift that occurs in such long term cultures how representative these cell lines are of breast cancer in vivo. For this reason primary cultures are generally regarded as a better model. Here we have used a primary culture technique (Int. J. Cancer, 66 (1996) 551; Br. J. Cancer, 78 (1998) 1421) to obtain primary breast cancer cells from 13 breast cancer biopsies. We then describe the development and use of methodology to confirm the purity of the cultures. The acquisition of a highly pure population of epithelial cells was confirmed by flow cytometric analysis of intracellular vimentin and cytokeratin 19. The methodology described will have many applications in studies requiring a highly pure population of epithelial breast cancer cells, as well as wide use in other cancers.
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PMID:Intracellular flow cytometric analysis of primary cultured breast tumor cells. 1202 29

To examine gene-expression patterning in late-stage breast cancer biopsies, we used a microdissection technique to separate tumor from the surrounding breast tissue or stroma. A DD-PCR protocol was then used to amplify expressed products, which were resolved using PAGE and used as probe to hybridize with representative human arrays and cDNA libraries. The probe derived from the tumor-stroma comparison was hybridized with a gene array and an arrayed cDNA library derived from a GCT of bone; 21 known genes or expressed sequence tags were detected, of which 17 showed differential expression. These included factors associated with epithelial to mesenchymal transition (vimentin), the cargo selection protein (TIP47) and the signal transducer and activator of transcription (STAT3). Northern blot analysis was used to confirm those genes also expressed by representative breast cancer cell lines. Notably, 6 genes of unknown function were restricted to tumor while the majority of stroma-associated genes were known. When applied to transformed breast cancer cell lines (MDA-MB-435 and T47D) that are known to have different metastatic potential, DD array analysis revealed a further 20 genes; 17 of these genes showed differential expression. Use of microdissection and the DD-PCR array protocol allowed us to identify factors whose localized expression within the breast may play a role in abnormal breast development or breast carcinogenesis.
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PMID:Differential gene expression in breast cancer cell lines and stroma-tumor differences in microdissected breast cancer biopsies revealed by display array analysis. 1211 66

Invasiveness and the capacity of tumor cells to form distant metastases are important cellular characteristics associated with a poor prognosis in breast cancer patients. In an approach to find genes that are potentially involved in these processes, RNA species showing different abundance in RNA pools from 12 invasive and 13 noninvasive mammary carcinoma-derived cell lines have been identified by hybridization to cDNA microarrays. CD24, keratin 19, keratin 8, GOB-4 and ezrin-radixin-moesin-binding phosphoprotein 50 were found to be preferentially expressed by noninvasive cells whereas vimentin was confirmed as a characteristic of invasive cells. Only differences in expression higher than 3-fold evident in three independent hybridization experiments were considered significant. For all cell lines, expression of mRNA coding for the adhesion molecule CD24, previously suggested to play an important role during tumor progression to more invasive phenotypes, has been quantified by real-time RT-PCR. Flow-cytometric analyses confirmed that CD24 mRNA reflects the amount of cell surface CD24 (Spearman R = 0.88, p = 10(-6)). CD24 mRNA was found to be absent or weakly expressed in 9/12 (75%) invasive cell lines compared to 3/13 (23%) noninvasive cell lines. The correlation between CD24 expression and invasiveness was calculated to be highly significant with chi2 = 6.74 and p = 0.0094. Future analyses of primary breast carcinomas are warranted to define the role of CD24 in future diagnostic and therapeutic approaches.
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PMID:Expression profiling of mammary carcinoma cell lines: correlation of in vitro invasiveness with expression of CD24. 1221 94

Overexpression of the oncogene HER2/neu (c-erbB-2) occurs in up to 30% of breast cancers and is correlated with reduced survival, especially in node-positive disease. The aim of this study was to identify genes associated with the aggressive phenotype of HER2/neu-positive breast cancer cells using cDNA microarrays. RNA was extracted from three HER2/neu-positive and three HER2/neu-negative breast cancer cell lines. Pooled RNA was hybridized in duplicate to the breast specific microarray filters from Research Genetics containing 5184 unique cDNAs. Subsequently, a similar comparison was performed for pooled RNAs from 10 node-positive, ER-positive invasive ductal carcinomas, half of which were HER2/neu overexpressers. In HER2/neu overexpressing breast cancer cell lines, 90 (1.7%) genes were up-regulated and 46 (0.9%) were down-regulated, compared to cell lines with low HER2/neu protein levels. In contrast, in HER2/neu overexpressing primary breast cancers, more genes were down-regulated (N = 132, 2.5%) than up-regulated (N = 19, 0.4%). Many of the differentially expressed genes have previously not been known to play a role in human neoplasia, and some of them may represent novel tumor suppressor or oncogenes. No genes were up-regulated, and only a small number of genes were down-regulated both in cell lines and in carcinomas with high HER2/neu protein levels. These included transforming acidic coiled-coil containing protein 1, glycogen phosphorylase BB, complement 1q and one EST. The differential expression of select genes was confirmed by Northern blotting (trefoil factor 3) or by immunocytochemistry (glycogen phosphorylase BB, vimentin, KAI1). In an extended validation study, 18 of 41 ER-negative, but none of 46 ER-positive, breast carcinomas were found to express vimentin, and all but one of the vimentin-positive tumors were confined to the HER2/neu-negative subgroup (P = 0.0019). Our findings support an important role of the mammary stroma in determining the clinical breast cancer phenotype.
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PMID:Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues. 1236 91

1,25-Dihydroxyvitamin D(3) (1,25D(3)), the active metabolite of vitamin D(3), inhibits breast cancer cell growth in vivo and in vitro. To examine mechanisms of 1,25D(3) induced growth arrest and apoptosis, cell lines were established from DMBA induced mammary tumors derived from vitamin D(3) receptor knockout (VDRKO) and wild type (WT) mice. Two VDRKO (KO240, KO288) and two WT (WT145, WT276) cell lines were selected and characterized. All four cell lines express cytokeratins indicative of an epithelial origin, as well as vimentin, which is expressed in many transformed cell lines. The tumorigenicity of the cells was confirmed in vivo as all four cell lines form estrogen responsive tumors in nude mice. Both WT cell lines express the VDR protein and are sensitive to growth inhibition by 1,25D(3) at doses as low as 1 nM. Flow cytometric analysis indicated that 1,25D(3) induces G(0)/G(1) arrest and apoptosis in the WT cell lines. In contrast, both cell lines established from tumors that developed in VDRKO mice lack VDR mRNA and protein. Cells from WT mice exhibit 1,25D(3) inducible transcriptional activity, as measured by reporter gene assays, but cells from VDRKO mice do not. Cells from VDRKO mice are also completely resistant to 1,25D(3) mediated growth arrest and apoptosis over the range of 0.01-100 nM 1,25D(3). VDRKO cells are also resistant to the synthetic vitamin D(3) analogs EB1089 and CB1093 that are more potent growth inhibitors than 1,25D(3) in WT cells. This data conclusively demonstrate that the induction of cell cycle arrest and apoptosis in breast cancer cells by 1,25D(3), EB1089 and CB1093 is dependent on the nuclear VDR. Cells lacking VDR remain sensitive to growth arrest mediated by 9-cis retinoic acid, a ligand for the retinoid x receptor which can heterodimerize with the VDR. Sensitivity to apoptosis induced by the DNA damaging agent etoposide is not altered in VDRKO cells, indicating that VDR ablation does not impair apoptotic pathways in general. All four cell lines display equal sensitivity to tamoxifen induced growth arrest. These estrogen responsive, transformed cell lines which differentially express the VDR provide a novel model system for identification of the mechanisms by which 1,25D(3) regulates proliferation and apoptosis in breast cancer cells.
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PMID:Characterization of mammary tumor cell lines from wild type and vitamin D3 receptor knockout mice. 1264

The cytoplasmic and nuclear redistribution of beta-catenin and the de novo expression of vimentin are frequently involved in the epithelial-to-mesenchymal transition associated with increased invasive/migratory properties of epithelial cells. Because beta-catenin can act as a coactivator of transcription through its binding to the T-cell factor (TCF)/lymphoid enhancer factor 1 transcription factor family, we have explored the possibility that beta-catenin/TCF could directly transactivate vimentin. We first compared vimentin expression in relation with the localization of beta-catenin in eight breast cancer cell lines displaying various degrees of invasiveness and in a model of cell migration using human mammary MCF10A cells. We could thus show a cytoplasmic and/or nuclear distribution of beta-catenin in invasive/migratory cells expressing vimentin, but not in noninvasive/stationary vimentin-negative cell lines. In addition, the human vimentin promoter was found to be up-regulated by beta-catenin and TCF-4 cotransfection. Varying with the cellular background, a diminution of this up-regulation was observed when the putative beta-catenin/TCF binding site of the vimentin promoter was mutated. Our results therefore demonstrate that the vimentin promoter is a target of the beta-catenin/TCF pathway and strongly suggest an implication of this regulation in epithelial cell migration/invasion.
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PMID:Transactivation of vimentin by beta-catenin in human breast cancer cells. 1275 Feb 94

Progesterone is an important regulator of growth and differentiation in breast tissues. In this study, the effect of progesterone on cell differentiation was evaluated in the estrogen receptor-negative and progesterone receptor (PR)-negative MDA-MB-231 cell line which was transfected with PR-complementary DNA. Morphological changes were analyzed at the ultrastructural level by scanning and transmission electron microscopy. Progesterone-treated PR-transfected cells exhibited a more protracted and well spread morphology with an increase in organelles such as mitochondria and rough endoplasmic reticulum as compared to the rounded form of control vehicle (0.1% ethanol)-treated PR-transfected cells. Vehicle and progesterone-treated MDA-MB-231 cells transfected with the pSG5 plasmid (transfection control cells) had similar rounded morphology as control vehicle-treated PR-transfected cells. Immunofluorescence staining revealed that expression of E-cadherin, a differentiation marker, was more prominent in progesterone-treated cells. Expression of keratin and vimentin but not beta-catenin was up-regulated in progesterone treated cells when evaluated by immunoblotting. As signal transducers and activators of transcription (STAT) molecules have been implicated in mammary differentiation, we analyzed the expression of Stat 1, 3, 5a, and 5b proteins and found a significant up-regulation of the Stat 5b protein in progesterone-treated cells. We have provided in vitro evidence of the close association of PR with differentiation in breast cancer. It is likely that the Stat 5b protein may play a major role in progesterone-induced differentiation in breast cancer cells.
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PMID:Progesterone induces cellular differentiation in MDA-MB-231 breast cancer cells transfected with progesterone receptor complementary DNA. 1275 36


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