Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pool of thyroids from wild type, E7 and RET-PTC tg mice at 2, 6 and 10 months

ABSTRACT: The RET/PTC3 (RP3) fusion gene is the most frequent mutation found in radiation-induced papillary thyroid cancers (PTC). Several studies suggest that the RET/PTC rearrangement is an initiating event in tumorigenesis. E7 is an oncoprotein derived from the Human Papilllomavirus 16 (HPV16) responsible for most cervical carcinoma in women. We studied here the sequence of events leading to thyroid cancer in Tg-RP3 and Tg-E7 mice expressing the transgene exclusively in the thyroid under the control of thyroglobulin (Tg) promoter. Both transgenic mice develop thyroid hyperplasia followed by solid differentiated carcinoma in older animals. To understand the different steps leading to carcinoma, we analyzed thyroid gene expression in both strains at different ages (2, 6, 10 months) by microarray technology. Important biological processes were differentially regulated in the two tumor types. In E7 thyroids cell cycle was the most upregulated process; observation consistent with the huge size of these tumors. In RP3 thyroids immunity was the most significantly regulated process, as previously observed in microarray data on human PTC. Interestingly, other human PTC characteristics were also observed in RP3 but not in E7 mouse tumors: similar regulation of several human PTC markers, upregulation of many EGF-like growth factors and finally significant regulation of angiogenesis and extracellular matrix remodeling-related genes. In summary we showed that RP3 contrary to E7 mouse tumors share several important genotypic characteristics with human PTC, observation reinforcing the validity of this model to study human thyroid tumorigenesis. Keywords: time course, genetic modification, disease state, cancer

ORGANISM(S): Mus musculus

PROVIDER: GSE10743 | GEO | 2008/07/18

SECONDARY ACCESSION(S): PRJNA107519

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Gene expression signature associated with BRAFV600E mutation in human papillary thyroid carcinoma based on transgenic mouse model (human)

Project description:BRAFV600E mutation is the most frequent molecular event in papillary thyroid carcinoma. The relation of this genetic alteration with the factors od poor prognosis has been reported as well as its influence on PTC gene signature. However human material disables distinction of cancer causes from its effect. We used our transgenic mouse model of papillary thyroid carcinoma induced by the BRAFV600E mutation to select BRAFV600E-specifi gene signature which was than compared to human material The human microarray data were obtained for: 27 papillary thyroid carcinomas including 18 BRAF(+), 8 RET(+), 1 RAS(+); 18 apparently healthy thyroids. In order to find BRAFV600E-specific gene signature data obtained from our transgenic mouse model of PTC were compared to human material. The analyses were performed taking into account not only the BRAF mutation but also other PTC initiating events including RET rearrangements and RAS poin mutations. Morover the microarray data were validated with the QPCR reaction.

2015-12-31 | E-GEOD-58545 | biostudies-arrayexpress

miRNA profile induced by RET/PTC1 oncogene in human thyrocytes

Project description:To obtain a PTC cell model, primary human thyrocytes have been infected with a retrovirus expressing RET/PTC1 oncogene, using parental thyrocytes as control. The obtained RET/PTC-dependent differential miRNA expression profile, representing the effects of RET/PTC1 oncogene present in about one third of papillary thyroid carcinoma (PTC), models the early event of thyrocytes transformation ending to PTC.

2014-06-30 | GSE49400 | GEO

miRNA profile induced by RET/PTC1 oncogene in human thyrocytes

2014-06-30 | E-GEOD-49400 | biostudies-arrayexpress

MicroRNA profiling of human papillary thyroid carcinoma and normal thyroid to assess the role of miRNA genes in papillary thyroid carcinoma

Project description:Apart from alterations in the RET/PTC-RAS-BRAF pathway, comparatively little is known about the genetics of papillary thyroid carcinoma (PTC). We show that numerous miRNAs are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of 5 miRNAs including the 3 most upregulated ones (miRs 221, 222, 146) distinguished unequivocally between PTC and normal thyroid. Additionally, miR-221 was upregulated in unaffected thyroid tissue in several PTC patients, presumably an early event in carcinogenesis. Tumors in which the upregulation (11-19 fold) of miRs 221, 222 and 146 was strongest showed dramatic loss of KIT transcript and Kit protein. In five of 10 such cases this was associated with germline single nucleotide changes in the two recognition sequences in KIT for these miRNAs. We conclude that upregulation of several miRs and down regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their downregulation.

2005-02-28 | E-TABM-68 | biostudies-arrayexpress

Mus musculus

Project description:pool of thyroids from wild type, E7 and RET-PTC tg mice at 2, 6 and 10 months

| PRJNA107519 | ENA

Normal thyrocytes vs papillary vs anaplastic thyroid carcinomas

Project description:We profiled the gene expression of 11 anaplastic thyroid carcinomas (ATC), 49 papillary thyroid carcinomas (PTC) and 45 normal thyroids (N)

2012-11-09 | GSE33630 | GEO

Gene expression profiling associated with the progression to poorly differentiated thyroid carcinomas

Project description:Poorly differentiated thyroid carcinomas (PDTC) represent a heterogeneous, aggressive entity, presenting features that suggest a progression from well-differentiated carcinomas. To elucidate the mechanisms underlying such progression and identify novel therapeutical targets, we assessed the genome-wide expression in normal thyroid tissues, well-differentiated thyroid carcinomas and PDTC. RNA were extracted from 2 normal thyroid tissues taken from the opposite lobe of thyroid tumors, and 24 thyroid carcinomas: 5 PDTC, 7 classic papillary thyroid carcinomas (cPTC), 8 follicular variants of PTC (fvPTC) and 4 follicular thyroid carcinomas (FTC). All samples were obtained at time of surgery and immediately frozen in liquid nitrogen. We also hybridized a commercial pool of human thyroid total RNA (BD Bioscience). PTC were screened for BRAF mutations and rearrangements of RET/PTC and, in addition, follicular variants were also analyzed for RAS mutations and PAX8-PPARG rearrangements. FTC were screened for RAS and PAX8-PPARG rearrangements. PDTC were analyzed for BRAF, RAS and PAX8-PPARG genes.

2013-12-10 | E-GEOD-53157 | biostudies-arrayexpress

Proteogenomics analysis unveils a novel TFG-RET gene fusion and druggable targets in papillary thyroid carcinomas

Project description:Papillary thyroid cancer (PTC) is the most common type of endocrine malignancy. From a set of PTC patients whose tumor did not harbour any BRAF or RAS mutations, a 35 years old male patient’s normal, primary tumor and lymph node (LN) metastatic tissues were subjected to genomics and proteomics analysis. By RNA-seq analysis, we identified a novel RET rearrangement involving exons 1-4 from the 5’ end of the Trk fused Gene (TFG) fused to the 3’ end of RET tyrosine kinase leading to a TFG-RET fusion which transforms immortalized human thyroid cells in a kinase-dependent manner. Further, TFG-RET oncogene oligomerises in a PB1 domain-dependent manner and consistently, mutation of the oligomerisation interface led to the inhibition of RET-mediated oncogenic transformation. Quantitative proteomic analysis of the same samples revealed the upregulation of proteins involved in the ubiquitination machinery including E3 Ubiquitin ligase HUWE1 and DUBs like USP9X and UBP7 in both tumor and LN metastatic lesions. We further identified that expression of TFG-RET led to the upregulation of HUWE1. Further, in a cohort of PTC patients, we observed higher expression of HUWE1, USP9X and USP7 in the tumor and metastatic lesions, when compared to the matched normal tissue. Transient knockdown of HUWE1, USP9X and USP7 affected viability and proliferation of TFG-RET transformed cells. Consistently, inhibition of RET, HUWE1 and DUBs by small molecule inhibitors significantly reduced RET-mediated oncogenesis. Apart from unveiling a novel oncogenic RET fusion in PTCs, our data may open a novel avenue of targeting ubiquitin signaling machinery in human PTCs.

2020-04-02 | PXD016828 | Pride

Gene expression signature associated with BRAFV600E mutation based on transgenic mouse model (mouse)

Project description:BRAFV600E mutation is the most frequent molecular event in papillary thyroid carcinoma. The relation of this genetic alteration with the factors od poor prognosis has been reported as well as its influence on PTC gene signature. However human material disables distinction of cancer causes from its effect. We used our transgenic mouse model of papillary thyroid carcinoma induced by the BRAFV600E mutation to select BRAFV600E-specific gene signature The transgenic mouse model was obtained by the microinjection of the transgene, composed of the human BRAF cDNA with V600E mutation under the control of bovine thyroglobulin, into the ferilized mice egg cells. Three lines were derived and mice after 4-24 months were sacrificed and histopathological evaluation of thyroids was carried out. In order to find BRAFV600E-specific gene signature microarray analysis was performed. The analysis invloved 38 mice thyroid samples: 10 mice papillary thyroid carcinomas, 10 borderline lesions (all being BRAF-positive), 10 apparently asymptomatic thyroids (5 BRAF-positive and 5 BRAF-negative) and 8 benign hyperplastic lesions (4 BRAF-positive and 4 BRAF-negative). Multofactoral analyses were performed in order to define some additional factors that could have impact on the gene expression profile.

2015-12-31 | E-GEOD-58546 | biostudies-arrayexpress

Murine: papillary thyroid cancer vs. poorly differentiated thyroid cancer

Project description:Mice with thyroid-specific expression of oncogenic BRAF (Tg-Braf) develop papillary thyroid cancers (PTC) that are locally invasive and have well-defined foci of poorly differentiated thyroid carcinoma (PDTC). To investigate the PTC-PDTC progression, we performed a microarray analysis using RNA from paired samples of PDTC and PTC collected from the same animals by laser capture microdissection. Analysis of 8 paired samples revealed a profound deregulation of genes involved in cell adhesion and intracellular junctions, with changes consistent with an epithelial-mesenchymal transition (EMT). This was confirmed by IHC, as vimentin expression was increased and E-cadherin lost in PDTC compared to adjacent PTC. Moreover, PDTC stained positively for phospho-Smad2, suggesting a role for transforming growth factor-beta (TGFbeta) in mediating this process. Accordingly, TGFbeta induced EMT in primary cultures of thyroid cells from Tg-Braf mice, whereas wild-type thyroid cells retained their epithelial features. TGFbeta-induced Smad2 phosphorylation, transcriptional activity and induction of EMT required MAPK pathway activation in Tg-Braf thyrocytes. Hence, tumor initiation by oncogenic BRAF renders thyroid cells susceptible to TGFbeta-induced EMT, through a MAPK-dependent process. Comparing the transcription profiles of 8 pairs of murine poorly differentiated thyroid cancer and papillary thyroid cancer collected from the same animals by laser capture microdissection. Co-hybridizations were done in triplicate with a single dye flip.

2011-03-22 | E-GEOD-27668 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data