Gene expression profiles of mammary epithelial and breast cancer cells following fever range hyperthermia
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Bryan Brad
PROVIDER: S-ECPF-GEOD-48398 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Preclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to “fever range” hyperthermia (increasing the intratumoral temperature to 42-45oC) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility. To address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray analysis of the global transcription changes was subsequently performed.
2013-12-01 | GSE48398 | GEO
Project description:Preclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to “fever range” hyperthermia (increasing the intratumoral temperature to 42-45oC) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility. To address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray analysis of the global transcription changes was subsequently performed. MCF10A (mammary epithelial cells) and MCF7, MDA231, and MDA468 breast cancer cells were grow at normal growth temperatures or subjected to 30 minutes of hyperthermic (45oC) shock followed by replacement with conditioned media at normal growth temperatures. RNA was collected 4 hours after shock and subjected to microarray analysis.
2013-12-01 | E-GEOD-48398 | biostudies-arrayexpress
Project description:Bovine mastitis is an inflammatory response of mammary glands caused by pathogenic microorganisms such as Escherichia coli (E. coli). As a key virulence factor of E. coli, lipopolysaccharide (LPS) triggers innate immune responses via activation of the toll-like-receptor 4 (TLR4) signaling pathway. However, the molecular regulatory network of LPS-induced bovine mastitis has yet to be fully mapped. In this study, bovine mammary epithelial cell lines MAC-T were exposed to LPS for 0, 6 and 12 h to assess the expression profiles of long non-coding RNAs (lncRNAs) using RNA-seq. Differentially expressed lncRNAs (DElncRNAs) were filtered out of the raw data for subsequent analyses. A total of 2,257 lncRNAs, including 210 annotated and 2047 novel lncRNAs were detected in all samples. A large proportion of lncRNAs were present in a high abundance, and 112 DElncRNAs were screened out at different time points. Compared with 0 h, there were 22 up- and 25 down-regulated lncRNAs in the 6 h of post-infection (hpi) group, and 27 up- and 22 down-regulated lncRNAs in the 12 hpi group. Compared with the 6 hpi group, 32 lncRNAs were up-regulated and 25 lncRNAs were down-regulated in the 12 hpi group. These DElncRNAs are involved in the regulation of a variety of immune-related processes including inflammatory responses bMECs exposed to LPS. Furthermore, lncRNA TCONS_00039271 and TCONS_00139850 were respectively significance down- and up-regulated, and their target genes involve in regulating inflammation-related signaling pathways (i.e.,Notch, NF-κB, MAPK, PI3K-Akt and mTOR signaling pathway), thereby regulating the occurrence and development of E. coli mastitis. This study provides a resource for lncRNA research on the molecular regulation of bovine mastitis.
| S-EPMC8589037 | biostudies-literature
Project description:BackgroundPreclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to "fever range" hyperthermia (increasing the intratumoral temperature to 42-45°C) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility.MethodsTo address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray, bioinformatics, and network analysis of the global transcription changes was subsequently performed.ResultsBioinformatics analysis differentiated the gene expression patterns that distinguish the heat shock response of normal cells from malignant breast cancer cells, revealing that the gene expression profiles of mammary epithelial cells are completely distinct from malignant breast cancer lines following this treatment. Using gene network analysis, we identified altered expression of transcripts involved in mitotic regulators, histones, and non-protein coding RNAs as the significant processes that differed between the hyperthermic response of mammary epithelial cells and breast cancer cells. We confirmed our data via qPCR and flow cytometric analysis to demonstrate that hyperthermia specifically disrupts the expression of key mitotic regulators and G2/M phase progression in the breast cancer cells.ConclusionThese data have identified molecular mechanisms by which breast cancer lines may exhibit enhanced susceptibility to hyperthermic shock.
| S-EPMC3931319 | biostudies-literature
Project description:cDNA microarrays and a clustering algorithm were used to identify patterns of gene expression in human mammary epithelial cells growing in culture and in primary human breast tumors. Clusters of coexpressed genes identified through manipulations of mammary epithelial cells in vitro also showed consistent patterns of variation in expression among breast tumor samples. By using immunohistochemistry with antibodies against proteins encoded by a particular gene in a cluster, the identity of the cell type within the tumor specimen that contributed the observed gene expression pattern could be determined. Clusters of genes with coherent expression patterns in cultured cells and in the breast tumors samples could be related to specific features of biological variation among the samples. Two such clusters were found to have patterns that correlated with variation in cell proliferation rates and with activation of the IFN-regulated signal transduction pathway, respectively. Clusters of genes expressed by stromal cells and lymphocytes in the breast tumors also were identified in this analysis. These results support the feasibility and usefulness of this systematic approach to studying variation in gene expression patterns in human cancers as a means to dissect and classify solid tumors.
| S-EPMC17759 | biostudies-literature
Project description:The female mammary epithelium undergoes reorganization during development, pregnancy, and menopause, linking higher risk with breast cancer development. To characterize these periods of complex remodeling, here we report integrated 50 K mouse and 24 K human mammary epithelial cell atlases obtained by single-cell RNA sequencing, which covers most lifetime stages. Our results indicate a putative trajectory that originates from embryonic mammary stem cells which differentiates into three epithelial lineages (basal, luminal hormone-sensing, and luminal alveolar), presumably arising from unipotent progenitors in postnatal glands. The lineage-specific genes infer cells of origin of breast cancer using The Cancer Genome Atlas data and single-cell RNA sequencing of human breast cancer, as well as the association of gland reorganization to different breast cancer subtypes. This comprehensive mammary cell gene expression atlas ( https://mouse-mammary-epithelium-integrated.cells.ucsc.edu ) presents insights into the impact of the internal and external stimuli on the mammary epithelium at an advanced resolution.
| S-EPMC8172904 | biostudies-literature
Project description:INTRODUCTION: Mammary stem cells are bipotential and suggested to be the origin of breast cancer development, but are elusive and vaguely characterized. Breast tumors can be divided into subgroups, each one requiring specific treatment. To determine a possible association between mammary stem cells and breast cancer, a detailed characterization of the transcriptome in mammary stem cells is essential. METHODS: We have used a murine mammary epithelial stem-like cell line (HC11) and made a thorough investigation of global gene-expression changes during stepwise differentiation using dual-color comparative microarray technique. Subsequently, we have performed a cross-species comparison to reveal conserved gene expression between stem cells and subtype-specific and prognosis gene signatures, and correlated gene expression to in vivo mammary gland development. RESULTS: Our analysis of mammary stem-like and stepwise cell differentiation, and an in-depth description of our findings in a breast cancer perspective provide a unique map of the transcriptomic changes and a number of novel mammary stem cell markers. We correlate the alterations to in vivo mammary gland differentiation, and describe novel changes in nuclear receptor gene expression. Interestingly, our comparisons show that specific subtypes of breast cancers with poor prognosis and metastasizing capabilities show resemblance to stem-like gene expression. CONCLUSIONS: The transcriptional characterization of these mammary stem-like cells and their differentiation-induced gene expression patterns is here made widely accessible and provides a basis for research on mammary stem-like cells. Our comparisons suggest that some tumors are more stem-like than others, with a corresponding worse prognosis. This information would, if established, be important for treatment decisions. We also suggest several marker candidates valuable to investigate further.
| S-EPMC2716494 | biostudies-literature
Project description:Microarray gene expression analysis was performed in MCF7 cells transduced with a non-specific shRNA or PDEF-targeting shRNA, and both subjected to hormone depletion for 48 hours. Analyses of differentially expressed genes combined with gene ontology revealed a downregulation of cell cycle related-genes and an upregulation of apoptosis-related genes in PDEF knockdown cells. These target genes constitute potential effectors of the pro-survival role of PDEF. Four samples were harvested after lentiviral infection with either non-specific shRNA control or PDEF-targetting shRNA. All samples were subjected to hormone depletion for 48 hours. Each condition was performed in duplicate
| S-ECPF-GEOD-40985 | biostudies-other
Project description:BackgroundSpontaneous immortalisation of cultured mammary epithelial cells (MECs) is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs) and the changes in gene expression associated with BME65Cs cells.ResultsBME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase) and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs) cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line). In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16INK4a was downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, DNMT1 is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of p53 and p16INK4a in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of p53 or p16INK4a.ConclusionsSpontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and exhibit non-malignant transformation. Although this cell line displays altered patterns of gene expression, it is clearly distinct from malignant breast cancer cell line. It showed that co-inhibition of cellular senescence and mitochondrial apoptosis pathways coordinates BME65Cs cells immortalisation. Additionally, mechanisms other than gene mutation are likely to be involved in regulation of cellular functions. This study provides an insight into the relationship between cell senescence and immortalisation. BME65Cs cells will be useful in future studies of cellular senescence and tumorigenesis.
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Project description:We have previously demonstrated that endoxifen is the most important tamoxifen metabolite responsible for eliciting the anti-estrogenic effects of this drug in breast cancer cells expressing estrogen receptor-alpha. The goals of this study were to compare the gene expression profiles elicited by endoxifen to that of other anti-estrogens in MCF7 cells. We also examined the gene expression profiles elicited by various endoxifen concentrations in the presence of tamoxifen and its other primary metabolites in order to better understand the molecular contributions of endoxifen to the effects of tamoxifen. Total RNA was isolated from parental MCF7 cells following 24 hour treatments with various individual or combined ligands. All studies were conducted in replicates of 3.
| S-ECPF-GEOD-43702 | biostudies-other