Gene expression profiles of triple-negative breast cancer cells under the condition of 3D proliferation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36953 | GEO | 2012/05/01
SECONDARY ACCESSION(S): PRJNA157283
REPOSITORIES: GEO
Similar Datasets
Project description:Triple-negative breast cancer (TNBC) is defined by the absence of estrogen and progesterone receptors and human epidermal growth factor receptor 2, and is the most lethal and aggressive subtype of breast cancer. However, the genes which relate to promote tumor aggressiveness in TNBC remain unclear. In order to investigate specific genes and pathways involved in TNBC tumorigenesis, we compared genes differentially expressed between 3D cultures (3DC) or tumor xenograft models and control two-dimensional cultures (2DC). Total RNA was prepared from the TNBC cells under the condition of 2DC, 3DC and tumor xenograft models, and applied to Affymetrix Human Genome U133 Plus 2.0 Array.
2012-04-30 | E-GEOD-36953 | biostudies-arrayexpress
Project description:The tumor suppressor menin has dual functions, acting either as a tumor suppressor or as an oncogene/oncoprotein, depending on the oncological context. Triple-negative breast cancer (TNBC) is characterized by lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 and is often a basal-like breast cancer. TNBC is associated with a dismal prognosis and an insufficient response to chemotherapies. Previously, menin was shown to play a proliferative role in ER-positive breast cancer; however, functions of menin in TNBC remains unknown. We have demonstrated that menin is expressed in various TNBC subtypes with the strongest menin expression in the TNBC Hs 578T cells. Depletion of menin by antisense oligonucleotide inhibited cell proliferation, enhanced apoptosis, and induced cell cycle arrest in Hs 578T cells, highlighting oncogenic functions of menin in this TNBC model. To better understand the menin function, we performed AP-MS (Affinity Purification-Mass Spectrometry) using specific antibody against menin. Analysis of menin interactome suggested that menin could drive TNBC tumorigenesis through regulation of the MLL/KMT2A-driven transcriptional activity, mRNA 3’ end processing and apoptosis.
2021-09-10 | PXD024176 | Pride
Project description:Cancer development and progression depend on tumor cell intrinsic factors, the tumor microenvironment and host characteristics. Despite the identification of the plasticity of adipocytes, the primary breast stromal cells, both in physiology and cancer, we lack a complete understanding of mechanisms that regulate adipocyte-tumor cell crosstalk. Here we dissected the breast cancer crosstalk with adipocytes and studied relevant molecules. We identified that the ability of breast cancer cells to dedifferentiate adipocytes is intrinsic subtype-dependent, with all breast cancer subtypes, except for HER2+ER+ subtype, capable of inducing this phenomenon. Crosstalk between breast cancer cells and adipocytes in vitro increased cancer stem-like features and recruitment of pro-tumorigenic immune cells, through chemokine production. Serum amyloid A1 (SAA1) was in vitro identified as a regulator of the adipocyte dedifferentiation program in triple-negative breast cancer (TNBC) through CD36 and P2XR7 signaling. In human TNBCs, SAA1 expression was associated with CAA infiltration, inflammation, stimulated lipolysis, stem-like properties and distinct tumor immune microenvironment. Our findings provide evidence that interaction between tumor cells and adipocytes through SAA1 release is relevant to the aggressiveness of TNBC, potentially supporting its targeting.
2024-01-15 | PXD041186 | Pride
Project description:Breast cancer is a heterogeneous disease comprised of four molecular subtypes defined by whether the tumor-originating cells are luminal or basal epithelial cells. Breast cancers arising from the luminal mammary duct often express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2). Tumors expressing ER and/or PR are treated with anti-hormonal therapies, while tumors overexpressing HER2 are targeted with monoclonal antibodies. Immunohistochemical detection of ER, PR, and HER2 receptors/proteins is a critical step in breast cancer diagnosis and guided treatment. Breast tumors that do not express these proteins are known as “triple negative breast cancer” (TNBC) and are typically basal-like. TNBCs are the most aggressive subtype, with the highest mortality rates and no targeted therapy, so there is a pressing need to identify important TNBC tumor regulators. The signal transducer and activator of transcription 3 (STAT3) transcription factor has been previously implicated as a constitutively active oncogene in TNBC. However, its direct regulatory gene targets and tumorigenic properties have not been well characterized. By integrating RNA-seq and ChIP-seq data from 2 TNBC tumors and 4 cell lines, we discovered novel gene signatures directly regulated by STAT3 that were enriched for processes involving inflammation, immunity, and invasion in TNBC. Functional analysis revealed that STAT3 has a key role regulating invasion and metastasis, a characteristic often associated with TNBC. Our findings suggest therapies targeting STAT3 may be important for preventing TNBC metastasis.
2017-06-10 | GSE85579 | GEO
Project description:Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). These receptors are well characterized and often serve as targets in breast cancer treatment. As a result, TNBCs are difficult to treat and have a high propensity to metastasize to distant organs. For these reasons, TNBCs are responsible for over 50% of all breast cancer mortalities while only accounting for 15% - 20% of breast cancer cases. However, estrogen receptor beta 1 (ERβ1) has emerged as a potential therapeutic target in the treatment of TNBCs. Using an in vivo xenograft preclinical mouse model with human TNBC, we found that expression of ERβ1 significantly reduced both primary tumor growth and metastasis in the animals. Moreover, TNBCs with elevated levels of ERβ1 showed reduction in epithelial-to-mesenchymal transition (EMT) markers and breast cancer stem cell (BCSC) markers, and increases in the expression of genes associated with inhibition of cancer cell invasiveness and metastasis, suggesting possible mechanisms underlying the antitumor activity of ERβ1. Treatment with ERβ1 agonist ligand often enhanced the suppressive activity of ERβ1, suggesting their potential utility in improving TNBC treatment. The findings enable understanding of the mechanisms by which ERβ impedes TNBC growth, invasiveness and metastasis and consideration of ways by which treatments involving ERβ might improve TNBC patient outcome.
2022-10-28 | GSE210092 | GEO
Project description:Breast cancer is genetically and clinically heterogeneous. Triple negative cancer (TNBC) is a subtype of breast cancer usually associated with poor outcome and lack of benefit from target therapy. A pathway analysis in a microarray study was performed using TNBC compared with non-triple negative breast cancer (non-TNBC). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 (FZD7), Low density lipoprotein receptor-related protein 6 (LRP6) and transcription factor 7 (TCF7) has been observed in TNBC. Focus was given to the Wnt pathway receptor, FZD7. To validate its function, inhibition of FZD7 using FZD7shRNA was carried out. Notably decreased cell proliferation, suppressed invasiveness and colony formation in triple negative MDA-MB-231 and BT-20 cells were observed. Mechanism study indicated that these effects occurred through silencing the canonical Wnt signaling pathway, as evidenced by loss of nuclear accumulation of ï?¢-catenin and decreased transcriptional activity of TCF7. In vivo study revealed that FZD7shRNA significantly suppressed the tumor formation in xenotransplation mice due to decrease cell proliferation. Our finding suggests that FZD7 involved canonical Wnt signaling pathway is essential for tumorigenesis of TNBC. Thus, FZD7 may be a biomarker and a potential therapeutic target for triple negative breast cancer. 14 pretreatment non-triple negative breast tumors compare with 5 triple negative breast tumor.
2011-06-01 | E-GEOD-27447 | biostudies-arrayexpress
Project description:The expression levels of JMJD6 and its correlation with H2A.XY39ph differed in TNBC and non-TNBC cells. In addition, we have previously shown that H2A.XY39ph levels are positively correlated with tumor size, histological grade and advanced TNM stage in breast cancer. To analyze the role of JMJD6 in regulating the characteristics of different subtypes of breast cancer, the transcriptomes of TNBC cells (SUM159) and non-TNBC cells (HCC1569) that overexpressed JMJD6 were compared. We speculate that JMJD6 overexpression cause autophagy pathway activation in TNBC via enhancing ATG genes expression.
2023-10-01 | E-MTAB-6517 | biostudies-arrayexpress
Project description:Lacking effective targeted therapies, triple-negative breast cancer (TNBCs) is highly aggressive, metastatic, and clinically challenging breast cancer subtype with worst prognosis. Despite survival dependency on the proteasome pathway genes, the FDA-approved proteasome inhibitors induced minimal clinical response in TNBC patients due to weaker proteasome inhibition. Here, we show that a novel proteasome inhibitor Marizomib (Mzb), inhibited multiple proteasome catalytic activities and induced better anti-tumor response in TNBC cell line and patient-derived xenografts alone and in combination with a standard-of-care chemotherapy, doxorubicin. Mechanistically, Mzb inhibits oxidative phosphorylation (OXPHOS) via PGC-1α suppression in conjunction with proteasome inhibition in TNBC cells. Development of metastatic disease, especially brain metastasis, remains a reason for a greater mortality rate amongst TNBC patients. Mzb reduces lung and brain metastasis in vivo by reducing circulating tumor cells and the expression of multiple epithelial-to-mesenchymal genes. We also demonstrate that Mzb-induced OXPHOS inhibition upregulates glycolysis to fulfill the metabolic demand of TNBC cells and hence, combined inhibition of glycolysis with Mzb leads to a synergistic anti-cancer activity in vivo. Collectively, our data provide a strong rationale for the clinical evaluation of Mzb in primary and metastatic TNBC patients.
2020-05-27 | PXD015141 | Pride
Project description:Breast cancer (BC) is the most common cancer in women worldwide, and is classified in multiple subtypes, including the so called triple-negative BC (TNBC). This is characterized by lack of estrogen receptor alpha (ERα), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), that represent common targets for BC treatment. Their absence limits the number of therapies that may be applied for TNBC treatment, suggesting the need to identify novel therapeutic targets against this disease. Several studies reported that the beta ER subtype (ERβ) is expressed in a sizeable fraction of TNBCs where its presence correlates with improved patient outcome. We evaluated ERβ expression in TNBC tissues by immunohistochemistry using two validated antibodies, demonstrating presence of this protein in 28% of samples. To investigate, in this context, the role of this estrogen receptor in TNBC biology, ERβ-expressing cell lines, representing different TNBC subtypes, were generated. Cellular and functional assays confirmed the antiproliferative activity of ERβ in TNBCs. Interaction proteomics revealed in BC nuclei the presence of several protein complexes associated with this receptor involved in chromatin remodeling, miRNA maturation and mRNA transcription. Transcriptome analyses pointed out tumor subtype-specific signaling pathways deregulation. Interestingly, among these the cholesterol biosynthesis pathway was commonly downregulated in all cell lines tested. Global analyses of ERβ binding to the genome showed its recruitment to regulatory sites of Sterol Regulatory Element-Binding Protein 1 (SREBP1), indicating a direct regulation of this pathway by the receptor. These findings suggest that drugs targeting components of cholesterol biosynthesis pathway may be new potential therapeutic options for TNBC treatment.
2019-12-03 | E-MTAB-8055 | biostudies-arrayexpress
Project description:Triple negative breast cancers (TNBC), defined by lacking the expression of oestrogen receptor-alpha (ERa), progesterone receptor, and HER2, is considered to be one of the most aggressive subtypes of all breast cancers. To elucidate the genomic and molecular aberrations in TNBC, we performed whole exon sequencing (WES) analysis on 36 TNBC, and identified 117 genes that significantly mutated (q < 0.05) in TNBC including MUC4, MUC6, TP53, and PIK3CA. Interestingly, genes associated with chromatin regulators including the subunits of SWI/SNF complex were frequently mutated in 44.7% of the cases. Furthermore, from the aspect of the possible association of epigenetic dysregulation and TNBC carcinogenesis, we focused on epigenome and genetic alterations of SALL3, an intrinsic inhibitor of DNMT3A, and identified the role of its dysfunction on cancer cell growth. Our study suggests that epigenetic aberrations caused by somatic alterations including DNA methylation might be a potential pathogenesis of TNBC in a certain number of cases.
2019-10-01 | GSE87479 | GEO