Effect of the expression of ELOVL5 and IGFBP6 genes on the metastatic potential of breast cancer cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE165854 | GEO | 2021/02/01
REPOSITORIES: GEO
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Project description:Identification of changes in protein expression by label-free shotgun proteomics in breast cancer MDA-MB-231 cells with knockdown of ELOVL5 and IGFBP6 genes in comparison with control MDA-MB-231 cells.
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Project description:Effect of the expression of ELOVL5 and IGFBP6 genes on the metastatic potential of breast cancer cells
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Project description:It has previously been reported that expression levels of insulin-like growth factor binding protein 6 (IGFBP6) are reduced in unstable plaques compared to stable plaques in patients with coronary heart disease (CAD). However, the exact role and mechanism of IGFBP6 in endothelial homeostasis and inhibition of focal atherosclerotic plaque development in vivo remains unclear. Transcripome sequencing and bioinformatics analysis of IGFBP6-overexpressed human umbilical vein endothelial cells (HUVECs) suggest that pathway analysis and differentially expressed mRNA may help clarify the role and potential mechanism of IGFBP6 in the treatment of cardiovascular diseases.
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Project description:Breast cancer line MDA-MB-231 was cultured in complete culture medium containing high glucose DMEM (4.5 g/L) supplemented with 10% fetal bovine serum, 2 mM L-glutamine and 1% antibiotic-antimycotic solution ( Gibco) in an MCO-18AC incubator (Sanyo, Japan) at 37ºC and 5% CO2 concentration in the air. Cell reseeding was carried out every 2-3 days according to the standard protocol. The protocol for obtaining the MDA-MB-231 cell line with stable knockdown of IGFBP6 was described previously (Nikulin et al., 2021).
2023-11-19 | GSE247735 | GEO
Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets. Thirteen simple mammary carcinomas with invasive growth and lymph node metastases at the time of tumor resection and 14 simple carcinomas without lymph node metastases were included in the study. None of the patients had radiographically detectable pulmonary metastases at the time of tumor resection. Distant metastases as the cause of death were determined postoperatively by radiographic detection of metastases or necropsy. Selection criteria for carcinomas without lymph node metastases included an invasive growth, a negative lymph node status, a histological grade III and a minimal tumor diameter above the average of the lymph node positive tumors (> 2.42 cm). All animals with non-metastatic carcinomas had a survival rate of over 24 months except animal no. 22 (2627) which developed radiographic detectable lung metastases 8 months after surgery. Tumor and lymph node histologies were evaluated independently by two board-certified pathologists, following the criteria of the WHO classification of canine mammary tumors and the Nottingham grading system. All 27 tumors were simple carcinomas and characterized by an invasive, mostly solid growth pattern, marked cellular pleomorphism, anisokaryosis and 3 or more mitotic figures per high power field.
2010-12-01 | E-GEOD-20718 | biostudies-arrayexpress
Project description:Metastasis of breast cancer to other distant organs is fatal to patients. However, few studies have revealed biomarkers associated with distant metastatic breast cancer. Furthermore, the inability of current biomarkers such as HER2, ER and PR, in accurately differentiating between distant metastatic breast cancers from non-distant metastatic ones necessitates the development of novel biomarkers. An integrated proteomics approach that combines filter-aided sample preparation, tandem mass tag labeling (TMT), high pH fractionation, and high resolution MS was applied to acquire in-depth proteome data of distant metastatic breast cancer FFPE tissue. Bioinformatics analyses for gene ontology and signaling pathways using differentially expressed proteins (DEPs) were performed to investigate molecular characteristics of distant metastatic breast cancer. In addition, real-time polymerase chain reaction (RT-PCR) and invasion/migration assays were performed to validate the differential regulation and functional capability of biomarker candidates. A total of 9,459 and 8,760 proteins were identified from the pooled sample set and the individual sample set, respectively. Through our stringent criteria, TUBB2A was selected as a novel biomarker. The metastatic functions of the candidate were subsequently validated. Bioinformatics analysis using DEPs were able to characterize the overall molecular features of distant metastasis as well as investigate the differences across breast cancer subtypes. Our study is the first to explore the distant metastatic breast cancer proteome using FFPE tissue. The depth of our dataset enabled the discovery of novel biomarker and the investigation of proteomic characteristics of distant metastatic breast cancer. The distinct molecular features of breast cancer subtypes were also observed. Our proteomic data has important utility as a valuable resource for the research on distant metastatic breast cancer.
2020-06-05 | PXD016061 | Pride
Project description:IGFBP6 is a secreted protein with a controversial role in human malignancies, being downregulated in the majority of human cancers, but upregulated in selected tumors. Ovarian carcinoma (OC) is a human malignancy characterized by IGFBP6 downregulation, even though the significance of its low expression during ovarian carcinogenesis is still poorly understood. IGFBP6 expression levels and the activation of its signaling pathway were evaluated in two matched OC cell lines derived from a high-grade serous ovarian cancer before and after platinum resistance (PEA1 and PEA2 cells,respectively). A whole genome gene expression analysis was comparatively performed in both cell lines upon IGFBP6 stimulation by Illumina technology. IGFBP6 gene expression in human OCs data were obtained from public datasets. Gene expression data from public datasets confirmed the downregulation of IGFBP6 from normal ovarian tissues to primary and metastatic OCs. The comparative analysis of platinum-sensitive (PEA1) and platinum-resistant (PEA2) cell lines showed quantitative and qualitative differences in the activation of IGFBP6 signaling. Indeed, IGFBP6 enhanced ERK1/2 phosphorylation only in PEA1 cells and induced a more evident and significant gene expression reprogramming in PEA1 compared to PEA2 cells. Furthermore, the analysis of selected genes modulated by IGFBP6 (i.e., FOS, JUN, TNF, IL6, IL8, and EGR1) showed an inverse regulation in PEA1 versus PEA2 cells, as well as selected hallmarks and IL-6 signaling were ositively regulated in PEA1, while inhibited in PEA2 cells.These data suggest that loss of IGFBP6 signaling may play a role in ovarian cancer progression, being likely associated to the development of platinum resistance.
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Project description:The development of metastases is a complex multi-step process manifested by diverse patterns, involving single or multiple organs and different time-courses of distant recurrences. The aim of this study was to characterise molecular patterns associated with patterns of organ-specific metastatic spread observed in the clinic from FFPE embedded breast carcinomas and lymph node metastases. This study includes patients with four patterns of first metastatic sites: bone only (with no visceral metastases within 6 months of first metastasis); to viscera only (with no bone metastasis within 6 months of first metastasis); to bone and visceral organs within a 6 month period; and no recorded distant metastasis. The study population was composed of 5,061 patients diagnosed with invasive primary breast cancer without distant metastasis at the time of diagnosis between 1975 and 2005 from Guyâs Hospital. From the study population, an incidence-based case-control design was used to include patients from each of the metastatic groups and a control series randomly matched to cases according to having no reported metastasis up to the calendar date of metastasis. The aim of this expression profiling study was to characterise any molecular patterns that may be associated with the organ-specific metastatic spread observed in the clinic from FFPE embedded breast carcinomas and lymph node metastases.
2017-12-01 | E-MTAB-4003 | biostudies-arrayexpress
Project description:Breast cancer in young patients is known to exhibit more aggressive biological behavior and is associated with a less favorable prognosis than the same disease in older patients, owing in part to an increased incidence of brain metastases, the mechanistic explanations behind which remain poorly understood. We recently reported that young mice, compared to older mice, showed about a three-fold increase in the development of brain metastases in mouse models of triple-negative and luminal B breast cancer. Here we have performed a quantitative mass spectrometry-based proteomic analysis to identify proteins contributing to age-related disparities in the development of breast cancer brain metastases. Using a mouse model of brain-tropic (MDA-MB-231BR) triple-negative breast cancer, we harvested subpopulations of tumor metastases, the tumor-adjacent metastatic microenvironment, and uninvolved brain tissues via laser microdissection followed by quantitative proteomic analysis using high resolution mass spectrometry to characterize differentially abundant proteins contributing to age-dependent rates of brain metastasis.
2024-01-11 | PXD042346 | Pride
Project description:Genome-wide DNA methylation profiling of brain metastases from lung cancer, breast cancer, and melanoma samples. The Illumina Infinium 450K Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 methylation sites in formalin-fixed paraffin-embedded (FFPE) samples from brain metastases. Samples included 30 breast cancer brain metastases, 18 lung cancer brain metastases, 37 melanoma brain metastases, and 4 samples with brain metastases from patients with uncertain primary.
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