Cytogenetic and cDNA Microarray Expression Analysis of MCF10 Human Breast Cancer Progression Cell Lines

Marella, Narasimharao V.; Malyavantham, Kishore S.; Wang, Jianmin; Matsui, Seiichi; Liang, Ping; Berezney, Ronald

doi:10.1158/0008-5472.can-09-0420

Cited by 45 publications

(46 citation statements)

References 44 publications

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“…Moreover, we identified large blocks of inter-chromosomal interactions between Chr 3 and Chr 5, Chr 3 and Chr 9, and Chr 6 and Chr 19, which represent previously known translocations in the MCF-10A genome (Supplemental Fig. S5; Marella et al 2009;Barutcu et al 2015). Taken together, these analyses reflect the high quality and reproducibility of the Hi-C data.…”

Section: Hi-c Analysis Of Smarca4 Knockdown and Control Mcf-10a Cellssupporting

confidence: 62%

SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells

et al. 2016

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The packaging of DNA into chromatin plays an important role in transcriptional regulation and nuclear processes. Brahmarelated gene-1 SMARCA4 (also known as BRG1), the essential ATPase subunit of the mammalian SWI/SNF chromatin remodeling complex, uses the energy from ATP hydrolysis to disrupt nucleosomes at target regions. Although the transcriptional role of SMARCA4 at gene promoters is well-studied, less is known about its role in higher-order genome organization. SMARCA4 knockdown in human mammary epithelial MCF-10A cells resulted in 176 up-regulated genes, including many related to lipid and calcium metabolism, and 1292 down-regulated genes, some of which encode extracellular matrix (ECM) components that can exert mechanical forces and affect nuclear structure. ChIP-seq analysis of SMARCA4 localization and SMARCA4-bound super-enhancers demonstrated extensive binding at intergenic regions. Furthermore, Hi-C analysis showed extensive SMARCA4-mediated alterations in higher-order genome organization at multiple resolutions. First, SMARCA4 knockdown resulted in clustering of intra-and inter-subtelomeric regions, demonstrating a novel role for SMARCA4 in telomere organization. SMARCA4 binding was enriched at topologically associating domain (TAD) boundaries, and SMARCA4 knockdown resulted in weakening of TAD boundary strength. Taken together, these findings provide a dynamic view of SMARCA4-dependent changes in higher-order chromatin organization and gene expression, identifying SMARCA4 as a novel component of chromatin organization.

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Section: Hi-c Analysis Of Smarca4 Knockdown and Control Mcf-10a Cellssupporting

confidence: 62%

SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells

et al. 2016

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“…Besides being frequently used in in vitro transformation assays MCF10A cell line was used for comprehensive analysis of the MCF10A series of cell lines representing progression towards recognizable malignancy [8], [9]. The MCF10A progression model consists of three directly derived cell lines: the spontaneously immortalized MCF10A cells (do not show any characteristics of invasiveness or tumor formation), MCF10AT1 cells (MCF10A cells transformed by HRAS), and MCF10CA1a cells (obtained from MCF10AT1 cells after xenograft transplantation in immune-deficient mice [8], [9]. Each of these cell lines showed specific quantitative chromosomal changes in addition to carrying a few common changes seen in all cell lines [13], [14].…”

Section: Functional Cell Line Groupingmentioning

confidence: 99%

“…Each of these cell lines showed specific quantitative chromosomal changes in addition to carrying a few common changes seen in all cell lines [13], [14]. Spectral karyotyping analysis showed that qualitative changes for example premalignant MCF10AT1 gained additional translocations to the MCF10A, whereas the malignant MCF10CA1a had more translocations than both MCF10A and MCF10AT1 [8]. Array comparative genome hybridization (aCGH) showed that MCF10A had a number of gains and losses of different chromosome regions and progression towards full malignancy was accompanied by much more widespread genomic aberrations.…”

Section: Functional Cell Line Groupingmentioning

confidence: 99%

“…[7]. The four MCF10A series of cell lines employed in this study represent breast cancer progression from near normal epithelial cells towards overt malignancy and have proven to be a powerful model to study breast cancer progression [8], [9]. Although in recent years there have been apparent advances and developments in understanding how free radical generation contributes to both progression and prognosis of breast cancer there still remains several basic unanswered questions.…”

Section: Introductionmentioning

confidence: 99%

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Threshold Effect of Free Radical Quenching in a Progressive Breast Cancer Cell Line Model

Sridharan¹,

Datta²,

Barhoumi³

et al. 2015

RBB

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Oxidative stress is a consequence of both normal and abnormal cellular metabolism and is linked to cell proliferation, differentiation and apoptosis leading to the development of human diseases. A common mechanism for chemotherapeutic agents inducing cell death is through the generation of free radicals. Although the exact mechanism of the molecular signalling that it entails is still being worked upon, it is clear that this varies with the stage and type of cancer and the drug and dosage used. We study the response of MCF10A series progressive breast cancer cell lines, in response to Adriamycin and Cyclophosphamide. A targeted set of candidate genes from these pathways that participate in free radical metabolism were evaluated for gene expression. Genes in oxidative stress response pathways were modelled earlier using the multivariate Boolean Network Modelling. We provide evidence that the strategy of using Boolean modelling and laboratory testing of the model, although not a perfect match, has potential to contribute in biology. We present a novel and testable "threshold" model of free radical generation that is dependent on the quantity of free radical generation. Using logic tools like Boolean circuitry, with fine-tuned experiments may serve a useful purpose in designing preclinical chemotherapic protocols.his document gives formatting instructions for authors preparing papers for publication in this journal. All authors must follow the instructions given in this document for the papers to be published.

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“…Our previous report demonstrated that expression of the LIF gene was upregulated during breast cancer progression in the isogenic MCF10 model (Rhee et al, 2008). The isogenic MCF10 human breast cancer model, which includes seven different cell lines originally derived from the same parent cell line, provides an opportunity to study breast cancer initiation, development, and progression (Hurst et al, 2009;Marella et al, 2009;Rhee et al, 2008;Santner et al, 2001;Worsham et al, 2006). In this study, we tested if increased expression of the LIF gene during progression to breast cancer could be correlated with changes in the DNA methylation pattern of its promoter region.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Up-Regulation of Leukemia Inhibitory Factor (LIF) Gene During the Progression to Breast Cancer

Shin

Park

Jang

2011

Molecules and Cells

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The interleukin 6 family of cytokines including leukemia inhibitory factor (LIF) regulates the progression of several types of cancer. However, although LIF overexpression during breast cancer progression was observed in our previous report, the molecular mechanisms responsible for this deregulation remain largely unknown. Here we show that LIF expression is epigenetically up-regulated via DNA demethylation and changes in histone methylation status within its promoter region in the isogenic MCF10 model. Bisulfite sequencing revealed the CpG pairs within the promoter region are hypermethylated in normal breast epithelial cells, but extensively demethylated as breast cancer progresses. In agreement with the DNA methylation pattern, our chromatin immunoprecipitation showed that inactive epigenetic marks such as MeCP2 occupancy and histone H3-Lys9-dimethylation significantly decreased during the progression to breast cancer but an active histone mark was increased in an inverse manner. Also, the occupancy of the transcription factor Sp1, which has higher affinity for hypomethylated CpGs, increased. RNAimediated knockdown of LIF expression resulted in a significant reduction of cell growth and colony formation in breast cancer cells, suggesting the potential role of LIF-LIF receptor axis in autocrine stimulation of cancer cells. Collectively, our data suggest that the epigenetic up-regulation of the LIF gene likely play an important role in the development of breast cancer.

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Cytogenetic and cDNA Microarray Expression Analysis of MCF10 Human Breast Cancer Progression Cell Lines

Cited by 45 publications

References 44 publications

SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells

SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells

Threshold Effect of Free Radical Quenching in a Progressive Breast Cancer Cell Line Model

Epigenetic Up-Regulation of Leukemia Inhibitory Factor (LIF) Gene During the Progression to Breast Cancer

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