Mammary Tissue: aCGH of primary (IGF-IR induced) and recurrent (IGF-IR independent) mammary tumors from MTB-IGFIR mice
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ABSTRACT:
PROVIDER: PRJNA491906 | ENA |
REPOSITORIES: ENA
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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: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:RNA was isolated from mammary glands from 55 day old control mice, mice overexpressing the miR-200b/200a/429 cluster in mammary epithelial cells (MTB-200ba429) mice overexpressing the IGF-IR transgene in mammary epithelial cells (MTB-IGFIR), and mice overexpressing both the miR-200b/200a/429 cluster and the IGF-IR transgene in mammary epithelial cells (MTB-IGFIRba429)
2021-09-17 | GSE180264 | GEO
Project description:Tumor recurrence represents a significant clinical challenge in the treatment and management of breast cancer. To investigate whether copy number aberrations (CNAs) facilitate the re-emergence of tumor growth from residual disease we performed array comparative genomic hybridization (aCGH) on primary and recurrent mammary tumors from an inducible mouse model of type-I insulin-like growth factor receptor (IGF-IR) driven breast cancer. This genome-wide analysis revealed primary and recurrent tumors harbored distinct copy number aberrations (CNAs) with relapsed tumors containing an increased number of gene-level gains and losses. Remarkably, CNAs detected in primary tumors were largely devoid of annotated cancer genes while the vast majority of recurrent tumors harbored at least one CNA containing a known oncogene or tumor suppressor. Specifically, a subset of recurrent tumors carried gains at 6qA2 and 9qA2 which encode the Met and Yap1 oncogenes respectively. The most frequent CNA detected was a focal deletion at 4qC5 involving the Cdkn2a and Cdkn2b tumor suppressor genes. Integrative analysis revealed positive correlations between gene copy number and mRNA expression suggesting Met, Yap1 and Cdkn2a/b may serve as potential driver genes that promote tumor recurrence. Together, these findings indicate that tumor recurrence is facilitated by the acquisition of CNAs with oncogenic potential and provide a framework to dissect the molecular mechanisms that mediate tumor escape from dormancy.
2018-11-28 | GSE120186 | GEO
Project description:Analysis of newborn mouse epidermis lacking the expression of Insulin receptor (IR) and Insulin like growth factor 1 receptor (IGF-1R). Results show that IR/IGF-1R signalling control epidermal morphogenesis.
2013-05-18 | GSE47065 | GEO
Project description:Analysis of newborn mouse epidermis lacking the expression of Insulin receptor (IR) and Insulin like growth factor 1 receptor (IGF-1R). Results show that IR/IGF-1R signalling control epidermal morphogenesis. RNA was isolated from newborn mouse epidermis.Gene expression profiling was on on Affymetrix 430-2.0 platform.
2013-05-18 | E-GEOD-47065 | biostudies-arrayexpress
Project description:The insulin-like growth factor (IGF) system consists of two ligands (IGF-I and IGF-II), which both signal through type I IGF receptor (IGF-IR) to stimulate proliferation and inhibit apoptosis, with activity contributing to malignant growth of many types of human cancers. We have developed a humanized, affinity-matured anti-human IGF-IR monoclonal antibody (h10H5), which binds with high affinity and specificity to the extracellular domain. h10H5 inhibits IGF-IR-mediated signaling by blocking IGF-I and IGF-IIbinding and by inducing cell surface receptor down-regulation via internalization and degradation. In vitro, h10H5 exhibits anti-proliferative effects on cancer cell lines. In vivo, h10H5 demonstrates single-agent anti-tumor efficacy in human SK-N-AS neuroblastoma and SW527 breast cancer xenograft models, and even greater efficacy in combination with the chemotherapeutic agent Docetaxel or an anti-VEGF antibody. Anti-tumor activity of h10H5 is associated with decreased AKT activation and glucose uptake, and a 316-gene transcription profile with significant changes involving DNA metabolic and cell cycle machineries. These data support the clinical testing of h10H5 as a biotherapeutic for IGF-IR-dependent human tumors. Keywords: Gene expression changes as markers for drug activity
2008-09-01 | GSE11959 | GEO
Project description:The insulin-like growth factor (IGF) system consists of two ligands (IGF-I and IGF-II), which both signal through type I IGF receptor (IGF-IR) to stimulate proliferation and inhibit apoptosis, with activity contributing to malignant growth of many types of human cancers. We have developed a humanized, affinity-matured anti-human IGF-IR monoclonal antibody (h10H5), which binds with high affinity and specificity to the extracellular domain. h10H5 inhibits IGF-IR-mediated signaling by blocking IGF-I and IGF-IIbinding and by inducing cell surface receptor down-regulation via internalization and degradation. In vitro, h10H5 exhibits anti-proliferative effects on cancer cell lines. In vivo, h10H5 demonstrates single-agent anti-tumor efficacy in human SK-N-AS neuroblastoma and SW527 breast cancer xenograft models, and even greater efficacy in combination with the chemotherapeutic agent Docetaxel or an anti-VEGF antibody. Anti-tumor activity of h10H5 is associated with decreased AKT activation and glucose uptake, and a 316-gene transcription profile with significant changes involving DNA metabolic and cell cycle machineries. These data support the clinical testing of h10H5 as a biotherapeutic for IGF-IR-dependent human tumors. Experiment Overall Design: Two treatment groups with four tumor samples per group are collected and analyzed,
2008-10-25 | E-GEOD-11959 | biostudies-arrayexpress
Project description:Although estrogen receptor (ER) and insulin-like growth factor (IGF) signaling are important for normal mammary development and breast cancer, cross-talk between these pathways, particularly at the level of gene transcription, remains poorly understood. We performed microarray analysis on MCF-7 breast cancer cells treated with estradiol (E2) or IGF-I for 3hr or 24hr. IGF-I regulated mRNA of 5-10-fold more genes than estradiol, and many genes were co-regulated by both ligands. Importantly, expression of these co-regulated genes correlated with poor prognosis of human breast cancer. Closer examination revealed enrichment of repressed transcripts. Interestingly, a number of potential tumor suppressors were down-regulated by IGF-I and estradiol. In fact, BLNK, one of the top repressed genes, is a potential growth suppressor in breast cancer cells. Analysis of three down-regulated genes showed that E2-mediated repression occurred independently of IGF-IR, and IGF-I-mediated repression occurred independently of ER. However, repression by IGF-I or estradiol required common downstream kinases. In conclusion, E2 and IGF-I co-regulate a set of genes that affect breast cancer outcome. There is enrichment of repressed transcripts, and the down-regulation is independent at the receptor level. This may be important clinically, as tumors with active ER and IGF-IR signaling may require co-targeting of both pathways. KEYWORDS: multiple group comparison
2011-05-09 | GSE26834 | GEO
Project description:Although estrogen receptor (ER) and insulin-like growth factor (IGF) signaling are important for normal mammary development and breast cancer, cross-talk between these pathways, particularly at the level of gene transcription, remains poorly understood. We performed microarray analysis on MCF-7 breast cancer cells treated with estradiol (E2) or IGF-I for 3hr or 24hr. IGF-I regulated mRNA of 5-10-fold more genes than estradiol, and many genes were co-regulated by both ligands. Importantly, expression of these co-regulated genes correlated with poor prognosis of human breast cancer. Closer examination revealed enrichment of repressed transcripts. Interestingly, a number of potential tumor suppressors were down-regulated by IGF-I and estradiol. In fact, BLNK, one of the top repressed genes, is a potential growth suppressor in breast cancer cells. Analysis of three down-regulated genes showed that E2-mediated repression occurred independently of IGF-IR, and IGF-I-mediated repression occurred independently of ER. However, repression by IGF-I or estradiol required common downstream kinases. In conclusion, E2 and IGF-I co-regulate a set of genes that affect breast cancer outcome. There is enrichment of repressed transcripts, and the down-regulation is independent at the receptor level. This may be important clinically, as tumors with active ER and IGF-IR signaling may require co-targeting of both pathways. KEYWORDS: multiple group comparison Microarray analysis on MCF-7 breast cancer cells treated with estradiol (E2) or IGF-I for 3hr or 24hr.
2011-05-09 | E-GEOD-26834 | biostudies-arrayexpress