Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA165159 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Murine models of mammary cancers have proven to be highly informative on numerous fronts including individual gene causation, microenvironmental analyses, and chemoprevention studies. The MMTV-Neu transgenic model of mammary cancer has proven to be a useful model and has been employed in several prevention studies. However, there are certain practical drawbacks to its use including long tumor latencies and a tendency to develop mutations in the transmembrane domain of Neu (unlike human HER2/Neu overexpressing breast cancers). Here we report modifications that were made in an attempt to optimize this mouse model for chemopreventive screening. First, homozygous MMTV-Neu and homozygous P53 KO mice were crossed to create a MMTV-Neu/P53+/- strain (which more closely approximates the genetic make-up of most HER2+ human patients). Second, to overcome the drawback of long tumor latencies, the mice were treated with DMBA for eight weeks. DMBA treatment greatly decreased the latency of mammary carcinomas in the MMTV-Neu mice although the resulting tumors remained histopathologically similar to those from MMTV-Neu control mice. Next, we examined gene expression in tumors derived from MMTV-Neu, MMTV-Neu/p53+/-, and DMBA treated mice. It was found that the characteristic MMTV-Neu tumor-defined expression pattern was still the most prevalent feature of all the MMTV-Neu tumors despite their being crossed to the p53 null allele, treated with DMBA, or both. However, tumors from the DMBA treated animals exhibited many unique gene expression changes including the high expression of stress response, defense, and inflammation genes. Finally, we demonstrated that the RXR agonists UAB30 and Targretin, both inhibited mammary cancer formation in MMTV-Neu mice, including those treated with DMBA. These results demonstrate the potential utility of this murine model for additional chemoprevention studies.
2021-01-31 | GSE35188 | GEO
Project description:Cancer is considered as a disease of a specific organ, but its effects are felt throughout the body. The systemic effects of cancer can lead to weakness in muscles and heart, which hastens cancer-associated death. miR-486 is a myogenic microRNA and its reduced expression in skeletal muscle is observed in muscular dystrophy. Muscle-specific transgenic expression of miR-486 using muscle creatine kinase promoter (MCK-miR-486) partially rescues skeletal muscle defects in muscular dystrophy animal models. We had previously demonstrated reduced circulating and skeletal muscle levels of miR-486 in several cancer types and lower miR-486 levels correlated with skeletal muscle defects and functional limitations in mammary tumor models. Therefore, skeletal muscle defects induced by cancer could resemble defects observed in various dystrophies, which could be reversed through skeletal muscle expression of miR-486. We performed functional limitations studies and biochemical analysis of skeletal muscles of MMTV-Neu transgenic mice that mimic HER2+ breast cancer and MMTV-PyMT transgenic mice that mimic luminal subtype B breast cancer and these mice crossed to MCK-miR-486 transgenic mice. miR-486 significantly prevented tumor-induced reduction in muscle contraction force, grip strength, and rotarod performance in MMTV-Neu, but not in MMTV-PyMT mice. In MMTV-Neu model, miR-486 reversed several of the cancer-induced changes in skeletal muscle including loss of p53, phospho-AKT, and phospho-laminin alpha 2 (LAMA2) and gain of phosphorylation of the pre-mRNA processing factor hnRNPA0 and the splicing factor SRSF10. LAMA2 is a part of the dystrophin-associated glycoprotein complex, and its loss-of-function mutation is associated with congenital muscular dystrophy. Thus, similar to muscular dystrophy, miR-486 has the potential to reverse skeletal muscle defects and cancer burden in select cancer types.
2022-05-19 | PXD028554 | Pride
Project description:To identify early events of erbB2-induced mammary tumorigenesis, we compared datasets from 14 genechip experiments including MMTV-neu tumors, preneoplastic neu mammary gland (adjacent neu), and age-matched, wild-type control mammary glands Keywords = transgenic mouse Keywords = MMTV-neu Keywords = erbB2 Keywords = HER2 Keywords = mammary tumor Keywords: ordered
2005-05-03 | GSE2528 | GEO
Project description:The role of Sca-1 on mammary tumorigenesis was assessed. Microarrays were used to analyse global gene expression changes in Sca-1 KO mice versus wild-type mice and determine the differential responses to MP and DMBA-induced Mammary carcinogenesis RNA was isolated (RNeasy Mini Kit, Qiagen) from MP-DMBA induced mammary tumor or mammary gland tissue from nulliparious transgenic and wild-type mice maintained on normal rodent chow
2011-09-09 | E-GEOD-31954 | biostudies-arrayexpress
Project description:The role of Sca-1 on mammary tumorigenesis was assessed. Microarrays were used to analyse global gene expression changes in Sca-1 KO mice versus wild-type mice and determine the differential responses to MP and DMBA-induced Mammary carcinogenesis
2011-09-10 | GSE31954 | GEO
Project description:To identify early events of erbB2-induced mammary tumorigenesis, we compared datasets from 14 genechip experiments including MMTV-neu tumors, preneoplastic neu mammary gland (adjacent neu), and age-matched, wild-type control mammary glands
2007-09-04 | E-GEOD-2528 | biostudies-arrayexpress
Project description:Gene expression profiling of samples from normal virgin mammary glands, hyperplastic mammary glands, mamary tumors, and lung metastases from MMTV-Wnt-1 transgenic (TG) mice, and mammary tumors and lung metastases from MMTV-Neu trangenic (TG) mice Keywords: Array analysis, multi-step tumorigenesis, metastasis, MMTV-Wnt-1 trangenic mice, MMTV-Neu transgenic mice
2005-09-30 | GSE2860 | GEO
Project description:Mice have been used as models for human breast cancers for many years, however, it is still unclear which murine models faithfully represent human tumor phenotypes. To address this question, we used DNA microarrays to characterize 10 different murine mammary models and compared these data to the expression patterns from primary human breast tumors. Hierarchical clustering analysis of the murine samples showed that the WAP-Myc, MMTV-Neu, MMTV-PyMT, WAP-Int3, and C3(1)-Tag tumors were highly correlated within each model. Other models, including the WAP-T_121 , MMTV-Wnt1, and DMBA-induced tumor model, did not show this consistency and gave rise to tumors with potentially different cell types of origin. A combined clustering analysis of the murine tumors with 102 human breast tumors showed many shared expression features. These features included a proliferation signature, an Interferon-regulated pattern, and patterns reflective of the presence of lymphocytes and fibroblasts. Murine tumors could be categorized according to their presumed cellular origins; the C3(1)-Tag, BRCA1+/-; p53+/-;IR, and DMBA-treated models displayed expression characteristics of human basal-like breast tumors; the MMTV-Neu, MMTV-PyMT, and WAP-Myc models shared features with human luminal breast tumors including the high expression of GATA3 and XBP1. In some cases, single mouse models did not reproduce the entire expression pattern seen in a specific human subtype; rather portions of a subtype’s expression profile were captured/represented by different murine models. The presence of shared patterns of expression between mice and humans provides a common framework for the direct comparison and integration of animal models with human breast Keywords: reference x sample
2007-05-01 | GSE3165 | GEO
Project description:To identify genes that may facilitate early steps of ErbB2/Neu-mediated mammary tumorigenesis, we performed comparative microarray analysis of 5- and 10-week bitransgenic mammary glands (LHxMMTV-neu) in triplicate. Keywords: transgenic mouse, erbB2, MMTV-neu, HER2, mammary tumor, breast cancer
2006-01-01 | GSE3501 | GEO
Project description:MMTV-NeuNT transgenic mouse model harbors an activated form of Neu (NeuNT). Mice develop stochastically multifocal mammary adenocarcinomas that metastasize to the lung (Muller et al., 1988). MMTV-NeuNT mouse model exhibits both intravascular and parenchymal metastasis which provides a good tool to comprehensively study breast cancer metastasis. In this study, we investigated the role of TNC in tumor progression using the MMTV-NeuNT mouse model. (3 MMTV-NeuNT TNC WT v/s 3 MMTV-NeuNT TNC KO). Breast tumor tissue were collected 3 months after first tumor palpation.
2021-02-11 | E-MTAB-10149 | biostudies-arrayexpress