Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA224138 | ENA |
REPOSITORIES: ENA
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Project description:BMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice. Breast cancer is a major cause of cancer related death in women, due to the development of metastatic disease in vital organs. Metastasis can be facilitated by tumor induced MDSC, which requires understanding. We have confirmed that BMP4 is a potent suppressor of breast cancer metastasis, but for potential clinical application, it is important to understand how BMP4 acts to suppress metastasis. Here, we report one mechanism by which BMP4 can inhibit metastasis. Mice bearing highly metastatic mammary tumors present with elevated numbers of myeloid derived suppressor cells (MDSC), the extent of which is markedly reduced upon exogenous BMP4 expression. Increased numbers of MDSC can also be induced directly by treatment with granulocyte-colony stimulating factor (G-CSF), leading to enhancement of metastasis. Both tumor-induced and G-CSF-induced MDSC can effectively suppress T cell activation and proliferation. BMP4 acts to reduce the expression and secretion of G-CSF through inhibition of NFkB activity in several human and mouse tumor lines. Since MDSC in breast cancer patients are correlated with poor prognosis, BMP4 treatment offers a potential new therapeutic strategy for progressive breast disease. Three 4T1.2 primary mammary tumours and three 4T1.2-Bmp4 primary mammary tumours were analyzed.
2014-06-01 | E-GEOD-51632 | biostudies-arrayexpress
Project description:BMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice. Breast cancer is a major cause of cancer related death in women, due to the development of metastatic disease in vital organs. Metastasis can be facilitated by tumor induced MDSC, which requires understanding. We have confirmed that BMP4 is a potent suppressor of breast cancer metastasis, but for potential clinical application, it is important to understand how BMP4 acts to suppress metastasis. Here, we report one mechanism by which BMP4 can inhibit metastasis. Mice bearing highly metastatic mammary tumors present with elevated numbers of myeloid derived suppressor cells (MDSC), the extent of which is markedly reduced upon exogenous BMP4 expression. Increased numbers of MDSC can also be induced directly by treatment with granulocyte-colony stimulating factor (G-CSF), leading to enhancement of metastasis. Both tumor-induced and G-CSF-induced MDSC can effectively suppress T cell activation and proliferation. BMP4 acts to reduce the expression and secretion of G-CSF through inhibition of NFkB activity in several human and mouse tumor lines. Since MDSC in breast cancer patients are correlated with poor prognosis, BMP4 treatment offers a potential new therapeutic strategy for progressive breast disease.
2014-06-01 | GSE51632 | GEO
Project description:To delineate gene expression levels in whole non-metastatic and metastatic transplantable primary mouse mammary tumour allografts Abstract to be provided from publication Primary mouse mammary tumours were grown till 400-600mm3 in size. Five different tumour models were analysed in triplicate. Thus, 3 different tumours/mice were used per model for a total of 15 mice. Each sample was applied to a separate microarray. Total RNA was prepared from whole primary tumours using Trizol reagent. Each sample was applied to Affymetrix gene expression arrays Mouse Gene 1.0ST.
2013-01-01 | E-GEOD-42272 | biostudies-arrayexpress
Project description:MiR-21 was identified as a gene whose expression correlated with the extent of metastasis of murine mammary tumours. Since miR-21 is recognized as being associated with poor prognosis in cancer, we investigated its contribution to mammary tumour growth and metastasis in tumours with capacity for spontaneous metastasis. Unexpectedly, we found that suppression of miR-21 activity in highly metastatic tumours resulted in regression of primary tumour growth in immunocompetent mice but did not impede growth in immunocompromised mice. Analysis of the immune infiltrate of the primary tumours at the time when the tumours started to regress revealed an influx of both CD4+ and CD8+ activated T cells and a reduction in PD-L1+ infiltrating monocytes, providing an explanation for the observed tumour regression. Loss of anti-tumour immune suppression caused by decreased miR-21 activity was confirmed by transcriptomic analysis of primary tumours. This analysis also revealed reduced expression of genes associated with cell cycle progression upon loss of miR-21 activity. A second activity of miR-21 was the promotion of metastasis as shown by the loss of metastatic capacity of miR-21 knockdown tumours established in immunocompromised mice, despite no impact on primary tumour growth. A proteomic analysis of tumour cells with altered miR-21 activity revealed deregulation of proteins known to be associated with tumour progression. The development of therapies targeting miR-21, possibly via targeted delivery to tumour cells, could be an effective therapy to combat primary tumour growth and suppress the development of metastatic disease.
2022-03-01 | GSE197520 | GEO
Project description:Dormancy of disseminated tumor cells in secondary organs leads to late breast cancer-related deaths after relapse. The bone marrow is one of the primary breast cancer metastatic sites and is associated with poor prognosis. Here, we investigated the role of major factors of the bone marrow, BMP4 and TGF?2, in regulating cancer cell dormancy. Unexpectedly, we observed that TGF?2 and BMP4 have a synergistic effect that induces dormancy in both normal and transformed mammary stem cells. Several assays (3D matrigel, FUCCI Cell Cycle Indicator) showed that co-exposure to TGF?2 and BMP4 had a stronger anti-proliferative effect than each ligand alone. In addition, transformed cells fully retained this synergistic effect while they became less sensitive to individual cytokines. Surprisingly, single-cell RNAseq analysis revealed the heterogeneity of the G0 compartment at the transcriptomic level. We identified a unique deep dormant cluster under TGF?2 and BMP4 co-exposure characterized by a blended signature from treatments by TGF?2 or BMP4 alone. These findings reveal that disseminated breast cancer cells in the bone marrow are placed in a deep dormant stage by the synergistic effect of TGF?2 and BMP4 that neither factor can achieve alone. Lastly, our data suggest that the local BMP4 levels decrease with tissue aging and can therefore contribute to dormant cell awakening. By providing a better understanding of BMP4/TGF?2 signaling, our results open opportunities to prevent cancer relapse.
2024-05-10 | GSE232164 | GEO
Project description:Gene expression profiling primary mouse mammary tumours from five different transplantable models
| PRJNA179511 | ENA
Project description:Molecular profiling was used to classify mammary tumors that develop in MTB-IGFIR transgenic mice. It was determined that the primary mammary tumors (PMT), which develop due to elevated expression of the type I insulin-like growth factor receptor (IGF-IR) in mammary epithelial cells, most closely resemble murine tumors with basal-like or mixed gene expression profiles and with human basal-like breast cancers. Downregulation of IGF-IR transgene in MTB-IGFIR tumor-bearing mice leads to the regression of most of the tumors followed by tumor re-appearance in some of the mice. These tumors that re-appear following IGF-IR transgene downregulation do not express the IGF-IR transgene and cluster with murine mammary tumors that express a mesenchymal gene expression profile and with human claudin-low breast cancers. Therefore, IGF-IR overexpression in murine mammary epithelial cells induces mammary tumors with primarily basal-like characteristics while tumors that develop following IGF-IR downregulation express a gene signature that most closely resembles human claudin-low breast tumors. Three conditions: 8 wild type (WT) mammary glands, 11 primary mammary tumor (PMT) samples, 9 recurrent spindle tumor (RST) samples, each sample was hybridized against a universal mouse reference RNA
2011-09-30 | E-GEOD-32152 | biostudies-arrayexpress
Project description:We explored the expression profile of circRNAs in canine mammary tumours using high-throughput sequencing technology. In our study, we analysed the expression profiles of 3 pairs of canine mammary tumours and their adjacent normal tissues. The total RNA was extracted, and a RNA library was constructed. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses revealed that these genes were mainly concentrated in 14 biological pathways. We selected 11 validated circRNAs and further confirmed the existence of these circRNAs by qRT-PCR. The circRNA-miRNA network diagram was constructed by using Cytoscape software. We found a total of 14851 circRNAs and 106 differentially expressed circRNAs in canine mammary tumours and their adjacent normal tissues (fold change ≥ 2, P ≤ 0.05). There were 64 upregulated circRNAs and 42 downregulated circRNAs. The main GO functions were the regulation of the regulated secretory pathway, the regulation of neurotransmitter secretion and the positive regulation of phagocytosis. Most of these pathways were related to the cGMP-PKG (cyclic guanosine monophosphate) signalling pathway, the cAMP (cyclic adenosine monophosphate) signalling pathway and the OXYTOCIN signalling pathway. CircRNAs have the function of adsorbing miRNA, similar to a sponge, and we further constructed the interaction network of circRNAs and miRNAs. The screened source genes closely related to canine mammary tumours included RYR2, PDE4D, ROCK2, CREB3L2 and UBA3. The screened circRNAs related to canine mammary tumours included chr27:26618544-26687235-, chr26:8194880-8201833+, and chr17:7960861-7967766-.In conclusion, our study uncovered circRNA expression profiles in canine mammary tumours. Moreover, some circRNAs may be used as potential biomarkers for screening dogs with high-risk canine mammary tumours.
2019-09-23 | GSE137825 | GEO
Project description:Molecular profiling was used to classify mammary tumors that develop in MTB-IGFIR transgenic mice. It was determined that the primary mammary tumors (PMT), which develop due to elevated expression of the type I insulin-like growth factor receptor (IGF-IR) in mammary epithelial cells, most closely resemble murine tumors with basal-like or mixed gene expression profiles and with human basal-like breast cancers. Downregulation of IGF-IR transgene in MTB-IGFIR tumor-bearing mice leads to the regression of most of the tumors followed by tumor re-appearance in some of the mice. These tumors that re-appear following IGF-IR transgene downregulation do not express the IGF-IR transgene and cluster with murine mammary tumors that express a mesenchymal gene expression profile and with human claudin-low breast cancers. Therefore, IGF-IR overexpression in murine mammary epithelial cells induces mammary tumors with primarily basal-like characteristics while tumors that develop following IGF-IR downregulation express a gene signature that most closely resembles human claudin-low breast tumors.
2011-10-01 | GSE32152 | GEO
Project description:Effect of BMP4 and noggin on gene expression in murine R1 ES cells
| PRJNA125141 | ENA