Gene expression profiles in BCPAP cells treated with BRAF inhibitors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE171483 | GEO | 2021/07/13
REPOSITORIES: GEO
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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
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
Project description:Anaplastic thyroid carcinoma (ATC) has among the worst prognosis of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. BRAF and TP53 mutations co-occur in a high proportion of ATC, particularly those associated with a precursor papillary thyroid carcinoma (PTC). In order to develop an adult-onset model of BRAF-mutant anaplastic thyroid carcinoma, we generated a novel thyroid-specific CreER transgenic mouse. We utilize a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from papillary to anaplastic thyroid carcinoma. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis and rapid lethality. We employed small animal ultrasound imaging to monitor autochthonous tumors, and show that treatment with the selective BRAF inhibitor PLX4720 improved survival, but did not lead to tumor regression or suppress signaling through the MAPK pathway. Combination of PLX4720 and the MEK inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines, and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. Total RNA from five murine papillary thyroid carcinoma (PTC) tumors and five murine anaplastic thyroid carcinoma (ATC) tumors was analyzed.
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Project description:Transcriptional profiling of human papillary thyroid cancer cells comparing control untreated BCPAP cells with BCPAP cells transfected with miR-145b-5p mimic. Two-condition experiment, BCPAP cells vs. miR-146b-5p transfexted BCPAP cells. Biological replicates: 1 control sample, 1 transfected sample.
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Project description:Transcriptional profiling of human papillary thyroid cancer cells comparing control untreated BCPAP cells with BCPAP cells transfected with miR-145b-5p mimic.
2015-12-17 | GSE76050 | GEO
Project description:Thyroid cancer is common, yet the sequence of alterations that promote tumor formation are incompletely understood. Here we describe a novel model of thyroid carcinoma in zebrafish that reveals temporal changes due to BRAFV600E. Through the use of real-time in vivo imaging we observe disruption in thyroid follicle structure that occurs early in thyroid development. Combinatorial treatment using BRAF and MEK inhibitors reversed the developmental effects induced by BRAFV600E. Adult zebrafish expressing BRAFV600E in thyrocytes developed invasive carcinoma. We identified a gene expression signature from zebrafish thyroid cancer that is predictive of disease free survival in patients with papillary thyroid cancer. Gene expression studies nominated TWIST2 as a key effector downstream of BRAF. Using CRISPR/Cas9 to genetically inactivate a TWIST2 orthologue, we suppressed the effects of BRAFV600E and restored thyroid morphology and hormone synthesis. These data suggest that expression of TWIST2 plays a role in an early step of BRAFV600E-mediated transformation.
2017-03-28 | GSE97096 | GEO
Project description:Anaplastic thyroid carcinoma (ATC) has among the worst prognosis of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. BRAF and TP53 mutations co-occur in a high proportion of ATC, particularly those associated with a precursor papillary thyroid carcinoma (PTC). In order to develop an adult-onset model of BRAF-mutant anaplastic thyroid carcinoma, we generated a novel thyroid-specific CreER transgenic mouse. We utilize a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from papillary to anaplastic thyroid carcinoma. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis and rapid lethality. We employed small animal ultrasound imaging to monitor autochthonous tumors, and show that treatment with the selective BRAF inhibitor PLX4720 improved survival, but did not lead to tumor regression or suppress signaling through the MAPK pathway. Combination of PLX4720 and the MEK inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines, and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma.
2014-04-02 | GSE55933 | GEO
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
2015-12-31 | GSE58546 | GEO
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
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
2015-12-31 | GSE58545 | GEO