Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA140431 | ENA |
REPOSITORIES: ENA
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Project description:We have previously shown that transgenic overexpression of the miR-200b/200a/429 cluster prevents mammary tumor development in MTB-IGFIR mice. In this study we evaluated whether the miR-200b/200a/429 cluster could also prevent mammary tumor development from a different oncogene, namely Neu/Erbb2. We found that transgenic overexpression of Neu/Erbb2 in MTB-TAN mice induce rapid mammary tumor development and co-overexpression of the miR-200b/200a/429 cluster with Neu/Erbb2 completely prevent mammary epithelial transformation and tumor development
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Project description:Perturbations in histone modifications alter transcription and promote carcinogenesis. Breast cancers frequently overexpress the histone methyltransferase EZH2, the catalytic subunit of Polycomb Repressor Complex 2 (PRC2). However, the mechanisms driving EZH2 overexpression are obscure and elucidating the role of PRC2 in breast cancer, which is highly heterogeneous, is challenging given its context-dependent oncogenic and tumor suppressive functions. Here, using genetically engineered mouse, PDX and cell line models, we show that the tyrosine kinase c-Src links energy sufficiency with PRC2 subunit overexpression via control of mRNA translation. In breast cancers initiated by the oncogene ErbB2, c-Src stimulates mitochondrial ATP production to suppress energy stress and permit sustained activation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which increases the translation of mRNAs encoding the PRC2 subunits Ezh2 and Suz12. We show that Ezh2 overexpression and activity are pivotal in ErbB2-mediated mammary tumorigenesis. These results reveal the hitherto unknown c-Src/mTORC1/PRC2 axis, which is essential for ErbB2-driven carcinogenesis.
2019-05-03 | GSE130661 | GEO
Project description:Perturbations in histone modifications alter transcription and promote carcinogenesis. Breast cancers frequently overexpress the histone methyltransferase EZH2, the catalytic subunit of Polycomb Repressor Complex 2 (PRC2). However, the mechanisms driving EZH2 overexpression are obscure and elucidating the role of PRC2 in breast cancer, which is highly heterogeneous, is challenging given its context-dependent oncogenic and tumor suppressive functions. Here, using genetically engineered mouse, PDX and cell line models, we show that the tyrosine kinase c-Src links energy sufficiency with PRC2 subunit overexpression via control of mRNA translation. In breast cancers initiated by the oncogene ErbB2, c-Src stimulates mitochondrial ATP production to suppress energy stress and permit sustained activation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which increases the translation of mRNAs encoding the PRC2 subunits Ezh2 and Suz12. We show that Ezh2 overexpression and activity are pivotal in ErbB2-mediated mammary tumorigenesis. These results reveal the hitherto unknown c-Src/mTORC1/PRC2 axis, which is essential for ErbB2-driven carcinogenesis.
2019-05-06 | GSE130738 | GEO
Project description:Perturbations in histone modifications alter transcription and promote carcinogenesis. Breast cancers frequently overexpress the histone methyltransferase EZH2, the catalytic subunit of Polycomb Repressor Complex 2 (PRC2). However, the mechanisms driving EZH2 overexpression are obscure and elucidating the role of PRC2 in breast cancer, which is highly heterogeneous, is challenging given its context-dependent oncogenic and tumor suppressive functions. Here, using genetically engineered mouse, PDX and cell line models, we show that the tyrosine kinase c-Src links energy sufficiency with PRC2 subunit overexpression via control of mRNA translation. In breast cancers initiated by the oncogene ErbB2, c-Src stimulates mitochondrial ATP production to suppress energy stress and permit sustained activation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which increases the translation of mRNAs encoding the PRC2 subunits Ezh2 and Suz12. We show that Ezh2 overexpression and activity are pivotal in ErbB2-mediated mammary tumorigenesis. These results reveal the hitherto unknown c-Src/mTORC1/PRC2 axis, which is essential for ErbB2-driven carcinogenesis.
2018-01-31 | GSE93892 | GEO
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 overexpressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas overexpression 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 profiles, we define the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amino acids synthesis (CBS, PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are upregulated, while genes involved in inflammatory response (SAA1, S100A7) are downregulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, miR-200b, miR-222, miR-221, miR-R210, and miR-424 are upregulated, while miR-27a, miR-27b, and miR-23b are downregulated. Overall, this study presents, for the first time, the gene expression changes underlying the invasive behavior following p130Cas overexpression in an ErbB2 transformed mammary cell model.
2013-07-22 | GSE42949 | GEO
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: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.
2013-08-01 | GSE43907 | GEO
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 overexpressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas overexpression 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 profiles, we define the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amino acids synthesis (CBS, PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are upregulated, while genes involved in inflammatory response (SAA1, S100A7) are downregulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, miR-200b, miR-222, miR-221, miR-R210, and miR-424 are upregulated, while miR-27a, miR-27b, and miR-23b are downregulated. Overall, this study presents, for the first time, the gene expression changes underlying the invasive behavior following p130Cas overexpression in an ErbB2 transformed mammary cell model. To identify transcriptional changes occurring during invasion we have performed a comparative microarray analysis of non coding RNA (miRNA) between MCF10A.B2 acini over-expressing p130Cas with activation of ErbB2 and control cells.
2013-07-22 | E-GEOD-42949 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) regulate a wide range of cellular signaling pathways and biological processes in both physiological and pathological states such as cancer. We have previously identified miR-135b as a direct regulator of androgen receptor (AR) protein level in prostate cancer (PCa). We wanted to further explore the relationship of miR-135b to hormonal receptors, particularly estrogen receptor α (ERα). Here we show that miR-135b expression inversely correlates with ER protein in two independent breast cancer (BCa) patient cohorts (101 and 1302 samples) and with AR protein in 47 PCa patient samples. We identify ERα as a novel miR-135b target by demonstrating miR-135b binding to the 3’UTR of the ERα and decreased ERα protein and mRNA level in breast cancer cells upon miR-135b overexpression. miR-135b inhibits proliferation of hormone receptor positive cancer cell lines as shown by overexpression in ERα-positive BCa cells (MCF-7) and AR-positive PCa cells (LNCaP, 22Rv1) when grown in 2D. To identify other genes regulated by miR-135b we performed gene expression studies and found a potential link to the hypoxia-inducible factor-1α (HIF1α) pathway. We show that miR-135b influences the protein level of the inhibitor for hypoxia-inducible factor-1 (HIF1AN), which also demonstrated an inverse correlation with miR-135b in a cohort of breast tumor samples. Taken together, our study demonstrates that miR-135b regulates ERα, AR and HIF1AN protein levels and proliferation in ERα -positive breast and AR-positive-prostate cancer cells.
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2017-02-09 | GSE73347 | GEO