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Gene expression profiling primary mouse mammary tumours from five different transplantable models

ABSTRACT: To delineate gene expression levels in whole non-metastatic and metastatic transplantable primary mouse mammary tumour allografts Abstract to be provided from publication

ORGANISM(S): Mus musculus

PROVIDER: GSE42272 | GEO | 2013/01/01

SECONDARY ACCESSION(S): PRJNA179511

REPOSITORIES: GEO

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Gene expression profiling primary mouse mammary tumours from five different transplantable models

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

Evolution of a transplantable cancer by adaptation

Project description:The histocompatibility barrier prevents transmission of both normal and tumour cells between individuals 1, however clonally transmissible cancers in dogs, Tasmania devils and soft-shell clams can naturally transmit as allografts 2. To understand how tumours can escape the histocompatibility barrier, we have serially passaged a mouse melanoma first into syngeneic mice and then into progressively more mismatched mouse strains until a fully allo-transplantable tumour emerged. Here we show that tumour passaging selected for cells with an anti-viral inflammatory signature, characterised by expression of MHC-I, PD-L1, Qa-1 non-classical MHC molecules and the upregulation of intergenic endogenous retroviral elements (ERVs). Knock-out of RNA sensor RIG-I 3 in the transplantable tumour cells resulted in reduced expression of MHC-I, PD-L1 and Qa-1. Antibody-mediated blockade of both PD-L1 and Qa-1 induced tumour regression after transplantation. A similar inflammatory signature was found in human melanomas that respond to anti-PD1 antibody treatment. Thus, an inflammatory anti-viral signature likely induced by RIG-I sensing of ERVs facilitates escape of the mouse melanoma from allogeneic rejection. The results underscore the immunological plasticity of melanoma and reveal an unanticipated role for inflammation in allograft immune evasion.

2025-07-29 | GSE288825 | GEO

Evolution of a transplantable cancer by adaptation [CTVT_RNAseq_cells]

2025-07-29 | GSE288897 | GEO

Evolution of a transplantable cancer by adaptation

Project description:Evolution of a transplantable cancer by adaptation

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Accurate determination of CRISPR-mediated gene fitness in transplantable tumours.

Project description:Assessing tumour gene fitness in physiologically-relevant model systems is challenging due to biological features of in vivo tumour regeneration, including extreme variations in single cell lineage progeny. Here we develop a reproducible, quantitative approach to pooled genetic perturbation in patient-derived xenografts (PDXs), by encoding single cell output from transplanted CRISPR-transduced cells in combination with a Bayesian hierarchical model. We apply this to 181 PDX transplants from 21 breast cancer patients. We show that uncertainty in fitness estimates depends critically on the number of transplant cell clones and the variability in clone sizes. We use a pathway-directed allelic series to characterize Notch signaling, and quantify TP53 / MDM2 drug-gene conditional fitness in outlier patients. We show that fitness outlier identification can be mirrored by pharmacological perturbation. Overall, we demonstrate that the gene fitness landscape in breast PDXs is dominated by inter-patient differences.

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Evolution of a transplantable cancer by adaptation [CTVT_RNAseq_cells]

Project description:Evolution of a transplantable cancer by adaptation [CTVT_RNAseq_cells]

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Serially transplantable mammary epithelial cells express the Thy-1 antigen.

Project description:BackgroundRecent studies in murine mammary tissue have identified functionally distinct cell populations that may be isolated by surface phenotype or lineage tracing. Previous groups have shown that CD24medCD49fhigh cells enriched for long-lived mammary epithelial cells can be serially transplanted.MethodsFlow cytometry-based enrichment of distinct phenotypic populations was assessed for their gene expression profiles and functional proliferative attributes in vitro and in vivo.ResultsHere, we show Thy-1 is differentially expressed in the CD24medCD49fhigh population, which allowed us to discern two functionally different populations. The Thy-1+CD24medCD49fhigh phenotype contained the majority of the serially transplantable epithelial cells. The Thy-1-CD24medCD49fhigh phenotype contains a rare progenitor population that is able to form primary mammary outgrowths with significantly decreased serial in vivo transplantation potential.ConclusionsTherefore, Thy-1 expression in the immature cell compartment is a useful tool to study the functional heterogeneity that drives mammary gland development and has implications for disease etiology.

| S-EPMC6180607 | biostudies-literature

Single-cell RNA profiling of mammary gland tumours in MMTV-PyMT mouse model of breast cancer.

Project description:Here, we use single cell sequencing to delineate the heterogeneity of tumours from the genetically engineered MMTV-PyMT mouse model of breast cancer (MMTV-PyMT::K14Cre::Rosa-tdTomato mice).

2024-05-08 | GSE159478 | GEO

Mapping and manipulating the M. tuberculosis transcriptome using a transcription factor overexpression-derived regulatory network

Project description:Expression data from transcription factor over expression experiments (Abstract from paper will be appended after publication)

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Gene expression profiling of a transplantable model of preneoplastic progression in mice using p53-null mammary epithelial cells

Project description:We show that macrophages are recruited to ductal hyperplasias that have a high tumor-forming potential where they are differentiated and polarized toward a tumor-promoting phenotype. These studies suggest that therapeutic targeting of tumor-promoting macrophages may not only be an effective strategy to block tumor progression and metastasis, but may also have critical implications for breast cancer prevention. To investigate mechanisms that drive tumorigenesis in early breast cancer progression, we employed a transplantable model of preneoplastic progression. Transplantation of p53-null mammary epithelial cells into the cleared mammary fad pads of syngeneic wildtype mice led to the formation of several premalignant lines that histologically and genetically recapitulated the various subtypes of human breast cancer. Two of these lines, PN1a and PN1b, were derived from contralateral outgrowths from the same mouse, and tissue from these outgrowths was serially transplanted for over 10 generations to confirm stability. At 16 weeks post-transplantation, PN1a lesions develop a poorly differentiated, lobuloalveolar morphology with multifocal regions of atypical cells in solid nests, while PN1b lesions remain low grade, ductal hyperplasia.

2017-06-04 | GSE84828 | GEO

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