Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Elevated expression of wildtype RhoC promotes ErbB2- and Pik3ca-induced mammary tumor formation

ABSTRACT: Copy number gains in genes coding for Rho activating exchange factors as well as losses affecting genes coding for RhoGAP proteins are common in breast cancer, suggesting that elevated Rho signaling may play an important role. Extra copies and overexpression of RhoC also occur, although a role for RhoC overexpression in driving tumor formation has not been assessed in vivo. To this end, we report on the development of a Rosa26 (R26)-targeted Cre-conditional RhoC overexpression mouse (R26-RhoC). This mouse was crossed to two models for ERBB2/NEU+ breast cancer: one based on expression of an oncogenic ErbB2/Neu cDNA downstream of the endogenous ErbB2 promoter (FloxNeoNeuNT), the other, a metastatic model that is based on high-level expression from MMTV regulatory elements (NIC). RhoC overexpression dramatically enhanced mammary tumor formation in FloxNeoNeuNT mice but showed a more subtle effect in the NIC line, which forms multiple mammary tumors after a very short latency. Many mammary tumors that form in FloxNeoNeuNT mice show selection for increased NeuNT expression linked to high-level amplification of the ErbB2/NeuNT locus. In contrast, NeuNT overexpression did not require high-level amplification of ErbB2/NeuNT in RhoC-FloxNeoNeuNT lesions. RhoC overexpression also enhanced mammary tumor formation in a model for breast cancer induced by Pik3ca(H1047R). The transforming effect of RhoC was associated with epithelial/mesenchymal transition (EMT) in ErbB2/NeuNT and Pik3ca-H1047R systems. Thus, RhoC copy number gains with resultant overexpression contribute to breast tumor formation and/or progression.

ORGANISM(S): Mus musculus

PROVIDER: GSE249601 | GEO | 2024/04/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression of ErbB2-positive tumors harboring either wild type p110α or H1047R mutation

Project description:A mouse model utilizing knock in strategy to coexpress both oncogenic ErbB2 (NeuNT) and a PI3KCA mutation H1047R Microarray was used to determine gene expression change due to H1047R mutation by comparison between ErbB2 KI tumors expressing either wild type or mutant allele.

2022-03-11 | GSE198377 | GEO

Comparative analysis of 10 week and 5 week Bitransgenic mice (LH mouse crossed with MMTV-neu mouse)

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

Transgenic overexpression of the miR-200b/200a/429 cluster prevents mammary tumor development in MTB-TAN mice

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

2024-08-26 | GSE270979 | GEO

Transcriptomic analysis investigating the role of TNC in tumor progression using the MMTV-NeuNT mouse model

2021-02-11 | E-MTAB-10149 | biostudies-arrayexpress

Comparative Analysis of MMTV-neu tumors, preneoplastic MMTV-neu mammary gland, and Wild-type controls

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

β-catenin signaling is a critical event in ErbB2-mediated mammary tumor progression.

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

Transcription profiling of cancer progression to study the intrinsic regulation of transforming growth factor-beta signaling in ErbB2/Neu-induced tumors

2007-09-04 | E-GEOD-2528 | biostudies-arrayexpress

RNA sequencing investigating the role of TNC in tumor progression using FVB TNC WT and TNC KO mice grafted with NT193 shC cells or NT193 shTNC cells

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 tenascin C (TNC) in tumor progression using the a syngeneic orthotopic grafting mouse model. NT193 cell line was isolated from MMTV-NeuNT TNC WT tumor tissue. TNC expression in these cells was turned down through shRNA strategy, giving rise to NT193 shTNC cells and their respective control NT193 shcTNC. These cells were grafted orthotopically into syngeneic FVB mice either WT or KO for TNC. In FVB WT mice, NT193 shcTNC tissue was treated with AMD3100 (plerixafor) (Sigma, A5602) at 5 mg/kg/day by peritumoral injection for 2 weeks before processing with NT193 shcTNC and NT193 shTNC tissue receiving phosphate buffered saline as a control.

2021-03-25 | E-MTAB-10135 | biostudies-arrayexpress

Reproductive history determines ErbB2 locus amplification, WNT signalling and tumor phenotype in a murine breast cancer model [exome sequencing]

Project description:Understanding the mechanisms underlying tumor heterogeneity is key to development of treatments that can target specific tumor subtypes. We have previously targeted CRE recombinase-dependent conditional deletion of the tumor suppressor genes Brca1, Brca2, p53 and/or Pten to basal or luminal ER- cells of the mouse mammary epithelium. We demonstrated that both the cell-of-origin and the tumor-initiating genetic lesions co-operate to influence mammary tumor phenotype. Here, we use a CRE-activated HER2 orthologue to specifically target HER2/ERBB2 oncogenic activity to basal or luminal ER- mammary epithelial cells and carry out a detailed analysis of the tumors which develop. We find that in contrast to our previous studies, basal epithelial cells are refractory to transformation by the activated NeuKI allele, with mammary epithelial tumor formation largely confined to luminal ER- cells. Histologically, the majority of tumors that developed were classified as either adenocarcinomas of no special type or metaplastic adenosquamous tumors. Remarkably, the former were more strongly associated with virgin animals and were typically characterised by amplification of the NeuNT/ErbB2 locus and activation of non-canonical WNT signalling. In contrast, tumors characterised by squamous metaplasia were associated with animals that had been through at least one pregnancy and typically had lower levels of NeuNT/ErbB2 locus amplification but had activated canonical WNT signalling. Squamous changes in these tumors were associated with activation of the Epidermal Differentiation Cluster. Thus, in this model of HER2 breast cancer, cell-of-origin, reproductive history, NeuNT/ErbB2 locus amplification, and the activation of specific branches of the WNT signalling pathway all interact to drive inter-tumor heterogeneity.

2020-12-01 | GSE162347 | GEO

Reproductive history determines ErbB2 locus amplification, WNT signalling and tumor phenotype in a murine breast cancer model [RNA-seq]

2020-11-12 | GSE161282 | GEO