Genn expression influenced by Akt1 knock out in mouse ErbB2 mammary tumor cells
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PROVIDER: PRJNA577885 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of ErbB2 mammary tumor cells derived from Akt1 wild type and knockout MMTV-ErbB2 transgenic mice using Affymetrix Mouse 430A v2.0 GeneChip arrays.
2020-12-08 | GSE138957 | GEO
Project description:The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.
2014-02-01 | GSE54582 | GEO
Project description:The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer. 214 MMTV-ErbB2 mammary tumors and 8 normal mammary glands were analyzed by Affymetrix microarrays.
2014-02-01 | E-GEOD-54582 | biostudies-arrayexpress
Project description:MicroRNAs regulated by lipopolysaccharide (LPS) target genes that contribute to the inflammatory phenotype. Here we showed that the protein kinase Akt1, which is activated by LPS, positively regulated miRNAs let-7e, miR-181c but negatively regulated miR-155 and miR-125b. In silico analyses and transfection studies revealed that let-7e repressed Toll-like receptor 4 (TLR4) whereas miR-155 repressed SOCS1, two proteins critical for LPS-driven TLR signalling, which regulate endotoxin sensitivity and tolerance. As a result, Akt1-/- macrophages exhibited increased responsiveness to LPS in culture and Akt1-/- mice did not develop endotoxin tolerance in vivo. Overexpression of let-7e and suppression of miR-155 in Akt1-/- macrophages restored sensitivity and tolerance to LPS in culture and in animals. These results indicate that Akt1 regulates the response of macrophages to LPS by controlling miRNA expression. The data deposited here contain the entire analysis of miRNA profile of Akt1+/+ and Akt1-/- thioglycollate elicited peritoneal macrophages following stimulation with LPS for 3 hours in culture.
2009-08-21 | GSE17421 | GEO
Project description:MicroRNAs regulated by lipopolysaccharide (LPS) target genes that contribute to the inflammatory phenotype. Here we showed that the protein kinase Akt1, which is activated by LPS, positively regulated miRNAs let-7e, miR-181c but negatively regulated miR-155 and miR-125b. In silico analyses and transfection studies revealed that let-7e repressed Toll-like receptor 4 (TLR4) whereas miR-155 repressed SOCS1, two proteins critical for LPS-driven TLR signalling, which regulate endotoxin sensitivity and tolerance. As a result, Akt1-/- macrophages exhibited increased responsiveness to LPS in culture and Akt1-/- mice did not develop endotoxin tolerance in vivo. Overexpression of let-7e and suppression of miR-155 in Akt1-/- macrophages restored sensitivity and tolerance to LPS in culture and in animals. These results indicate that Akt1 regulates the response of macrophages to LPS by controlling miRNA expression. The data deposited here contain the entire analysis of miRNA profile of Akt1+/+ and Akt1-/- thioglycollate elicited peritoneal macrophages following stimulation with LPS for 3 hours in culture. Thioglycollate elicited macrophages were cultured in complete DMEM medium, stimulated with LPS for 3 hours and RNA was extracted. Samples were analyzed using Taq-man PCR miRNA arrays (Dana Farber microarray Facility).
2009-08-21 | E-GEOD-17421 | biostudies-arrayexpress
Project description:Although ERBB2 amplification and overexpression is correlated with poor outcome in breast cancer, the molecular mechanisms underlying the aggressive nature of these tumors has not been fully elucidated. To investigate this further, we have used a transgenic mouse model of ErbB2-driven tumor progression (ErbB2KI model) that recapitulates clinically relevant events, including selective amplification of the core erbB2 amplicon. By comparing the transcriptional profiles of ErbB2KI mammary tumors and human ERBB2-positive breast cancers, we demonstrate that ErbB2KI tumors possess molecular features of the basal subtype of ERBB2-positive human breast cancer, including activation of canonical β-catenin signaling. Inhibition of β-catenin-dependent signaling in ErbB2KI-derived tumor cells using RNA interference impaired tumor initiation and metastasis. Furthermore, treatment of ErbB2KI or human ERBB2-overexpressing tumor cells with a selective β-catenin/CBP inhibitor significantly decreased proliferation and ErbB2 expression. Collectively, our data indicate that ERBB2-mediated breast cancer progression requires β-catenin signaling and can be therapeutically targeted by selective β-catenin/CBP inhibitors.
2013-06-02 | GSE37954 | GEO
Project description:Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays a critical role in the regulation of several cellular processes including cell proliferation and apoptosis. In this study, we utilized Akt1+/+ and Akt1¬-/- C57/Bl6 female mice to demonstrate that Akt1 is required for normal mammary gland postnatal development and homeostasis. Akt1 deficiency resulted in severely delayed postnatal mammary gland growth as well as a significant decrease in the number of terminal end buds during puberty. Adult Akt1-/- mammary glands exhibited significantly fewer alveolar buds coupled with a significant increase in epithelial cell apoptosis compared to their wild-type counterparts. Microarray analysis revealed that Akt1 deficiency resulted in several altered gene expression changes and biological processes in adult mammary glands, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1-/- mammary glands by both microarray and RT-PCR validation. Transcriptome analysis of Akt1 wild type and akt1-homozygous mouse mammary glands
2011-07-15 | GSE30671 | GEO
Project description:Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays a critical role in the regulation of several cellular processes including cell proliferation and apoptosis. In this study, we utilized Akt1+/+ and Akt1¬-/- C57/Bl6 female mice to demonstrate that Akt1 is required for normal mammary gland postnatal development and homeostasis. Akt1 deficiency resulted in severely delayed postnatal mammary gland growth as well as a significant decrease in the number of terminal end buds during puberty. Adult Akt1-/- mammary glands exhibited significantly fewer alveolar buds coupled with a significant increase in epithelial cell apoptosis compared to their wild-type counterparts. Microarray analysis revealed that Akt1 deficiency resulted in several altered gene expression changes and biological processes in adult mammary glands, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1-/- mammary glands by both microarray and RT-PCR validation. Transcriptome analysis of Akt1 wild type and akt1-homozygous mouse mammary glands wild type mammary glands from 3 mice and Akt1-deficient mammary glands from 3 mice were analyzed for differences in gene expression at postnatal day 70
2011-07-14 | E-GEOD-30671 | biostudies-arrayexpress
Project description:Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. It is well known that ErbB2 is over-expressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas over-expression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in three-dimensional (3D) cultures of human mammary epithelial cells. Here, by comparing coding and non-coding gene expression profiling, we define the invasive signatures associated with concomitant p130Cas over-expression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amminoacids synthesis (CBS and PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are up-regulated while genes involved in the inflammatory response (SAA1, S100A7) are down-regulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, mir-200b, miR-222, miR-221and miR-424 are up-regulated while miR-27a, miR-27b and miR-23b are down-regulated. Overall this study present, for the first time, gene expression changes underlying the invasive behaviour following p130Cas over-expression in an ErbB2 transformed mammary cell model. 12 samples were analyzed: 3 ErbB2, 3 Cas, 3 Cas/ErbB2, 3 Ctr MCF10A.B2
2013-08-01 | E-GEOD-43907 | biostudies-arrayexpress
Project description:Although ERBB2 amplification and overexpression is correlated with poor outcome in breast cancer, the molecular mechanisms underlying the aggressive nature of these tumors has not been fully elucidated. To investigate this further, we have used a transgenic mouse model of ErbB2-driven tumor progression (ErbB2KI model) that recapitulates clinically relevant events, including selective amplification of the core erbB2 amplicon. By comparing the transcriptional profiles of ErbB2KI mammary tumors and human ERBB2-positive breast cancers, we demonstrate that ErbB2KI tumors possess molecular features of the basal subtype of ERBB2-positive human breast cancer, including activation of canonical β-catenin signaling. Inhibition of β-catenin-dependent signaling in ErbB2KI-derived tumor cells using RNA interference impaired tumor initiation and metastasis. Furthermore, treatment of ErbB2KI or human ERBB2-overexpressing tumor cells with a selective β-catenin/CBP inhibitor significantly decreased proliferation and ErbB2 expression. Collectively, our data indicate that ERBB2-mediated breast cancer progression requires β-catenin signaling and can be therapeutically targeted by selective β-catenin/CBP inhibitors. Common reference design. 9 samples (including 2 normal tissue, 2 NIC tumors, and 5 KI tumor tissue samples) replicated twice as dye swaps, generating a total of 18 arrays.
2013-06-02 | E-GEOD-37954 | biostudies-arrayexpress