Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA141575 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Characterization of neuroendocrine tumors in heterozygous mutant MENX rats: a novel model of invasive medullary thyroid carcinoma [thyroid]
| PRJNA385488 | ENA
Project description:CDKN1B (p27) was formally established as a tumor suppressor gene (tsg) following the identification of inactivating germline mutations in rats (MENX syndrome) and patients (MEN4 syndrome) developing multiple neuroendocrine tumors (NETs). MENX-affected rats are homozygous for the predisposing p27 mutation, suggesting a canonical tsg function. In contrast, mice heterozygous for a defective Cdkn1b allele are already predisposed to tumor formation (haploinsufficiency). We here report that heterozygous mutant rats (p27+/mut) develop the same NETs seen in the homozygous (p27mut/mut) animals but with slower progression. In the tumors of p27+/mut rats, the wild-type allele is neither lost nor silenced, implying that p27 is haploinsufficient for tumor suppression also in this model. Transcriptome profiling of rat NETs having different p27 dosages revealed a tissue-specific, dose-dependent effect of p27 on gene expression. In p27+/mut rats, thyroid neoplasms progress to invasive and metastatic medullary thyroid carcinomas (MTCs) accompanied by increased calcitonin levels, as in humans. Comparison of expression signatures of late-stage versus early-stage MTCs from p27+/mut rats identified genes potentially involved in tumor aggressiveness. The expression of a subset of these genes was evaluated in human MTCs, and found associated with aggressive RET-M918T-positive tumors. Altogether, p27 haploinsufficiency in MENX rats uncovered a novel, representative model of invasive/metastatic MTC, exploitable for translational studies of this aggressive and often incurable cancer.
2017-11-15 | GSE98546 | GEO
Project description:Characterization of neuroendocrine tumors in heterozygous mutant MENX rats: a novel model of invasive medullary thyroid carcinoma [adrenal]
| PRJNA231843 | ENA
Project description:As overwhelming evidence coming from transgenic mouse models but also from MEN4 patients seem to suggest that loss or inactivation of a single p27 allele plays an important role in neuroendocrine tumorigenesis, we decided to perform a detailed analysis of the phenotype of rats heterozygous for the MENX-associated germline Cdkn1b mutation. We here show that the reduction to a single functional p27 allele predisposes MENX heterozygous rats to the development of neuroendocrine malignancies.
2017-11-15 | GSE29457 | GEO
Project description:As overwhelming evidence coming from transgenic mouse models but also from MEN4 patients seem to suggest that loss or inactivation of a single p27 allele plays an important role in neuroendocrine tumorigenesis, we decided to perform a detailed analysis of the phenotype of rats heterozygous for the MENX-associated germline Cdkn1b mutation. We here show that the reduction to a single functional p27 allele predisposes MENX heterozygous rats to the development of neuroendocrine malignancies.
2017-11-15 | GSE53365 | GEO
Project description:Transcriptional analysis of 49 primary medullary thyroid carcinoma tumors. Comparisons MTCM918T vs MTC634 and MTCM918T vs MTCWT. 49 (52 hybridized tumors with 3 replicates) primary Medullary Thyroid Carcinoma (MTC) cases were hybridized onto a cDNA microarray in order to identify the unique markers for specific genetic classes of MTC.
2013-11-26 | E-GEOD-32662 | biostudies-arrayexpress
Project description:The radiolabelled somatostatin analogue 177Lu-octreotate is a promising treatment option for malignant neuroendocrine tumors that overexpress somatostatin receptors. The human small intestine neuroendocrine tumor cell line GOT1 and Medullary thyroid carcinoma model GOT2 have shown promising treatment response to 177Lu-octreotate in xenografted mice. In clinical studies, however, only low cure rates have been achieved to date. In xenografted tumors, the human stromal components have been replaced with mouse stroma, which may have an impact in the treatment response of the xenografts.
2017-12-31 | GSE80021 | GEO
Project description:Transcriptional analysis of 49 primary medullary thyroid carcinoma tumors. Comparisons MTCM918T vs MTC634 and MTCM918T vs MTCWT.
2013-11-26 | GSE32662 | GEO
Project description:Gonadotroph adenomas comprise 15M-bM-^@M-^S40 % of all pituitary tumors, are usually non-functioning and are often large and invasive at presentation. Surgery is the first-choice treatment, but complete resection is not always achieved, leading to high recurrence rates. As gonadotroph adenomas poorly respond to conventional pharmacological therapies, novel treatment strategies are needed. Their identification has been hampered by our incomplete understanding of the molecular pathogenesis of these tumors. Recently, we demM-BM-,onstrated that MENX-affected rats develop gonadotroph adenomas closely resembling their human counterparts. To discover new genes/pathways involved in gonadotroph cells tumorigenesis, we performed transcriptome profiling of rat tumors versus normal pituitary. Adenomas showed overrepM-BM-,resentation of genes involved in cell cycle, development, cell differentiation/proliferation, and lipid metabolism. BioinforM-BM-,matic analysis identified downstream targets of the transcripM-BM-,tion factor SF-1 as being up-regulated in rat (and human) adenomas. Meta-analyses demonstrated remarkable similariM-BM-,ties between gonadotroph adenomas in rats and humans, and highlighted common dysregulated genes, several of which were not previously implicated in pituitary tumorigenesis. Two such genes, CYP11A1 and NUSAP1, were analyzed in 39 human gonadotroph adenomas by qRT-PCR and found to be up-regulated in 77 and 95 % of cases, respectively. Immunohistochemistry detected high P450scc (encoded by CYP11A1) and NuSAP expression in 18 human gonadoM-BM-,troph tumors. In vitro studies demonstrated for the first time that Cyp11a1 is a target of SF-1 in gonadotroph cells and promotes proliferation/survival of rat pituitary adenoma priM-BM-,mary cells and cell lines. Our studies reveal clues about the molecular mechanisms driving rat and human gonadotroph adenomas development, and may help identify previously unexplored biomarkers for clinical use. We compared five control animals and 16 homozygous mutants (p27Kip1/Cdknb1)
2013-07-10 | E-GEOD-23207 | biostudies-arrayexpress
Project description:Gonadotroph adenomas comprise 15–40 % of all pituitary tumors, are usually non-functioning and are often large and invasive at presentation. Surgery is the first-choice treatment, but complete resection is not always achieved, leading to high recurrence rates. As gonadotroph adenomas poorly respond to conventional pharmacological therapies, novel treatment strategies are needed. Their identification has been hampered by our incomplete understanding of the molecular pathogenesis of these tumors. Recently, we dem¬onstrated that MENX-affected rats develop gonadotroph adenomas closely resembling their human counterparts. To discover new genes/pathways involved in gonadotroph cells tumorigenesis, we performed transcriptome profiling of rat tumors versus normal pituitary. Adenomas showed overrep¬resentation of genes involved in cell cycle, development, cell differentiation/proliferation, and lipid metabolism. Bioinfor¬matic analysis identified downstream targets of the transcrip¬tion factor SF-1 as being up-regulated in rat (and human) adenomas. Meta-analyses demonstrated remarkable similari¬ties between gonadotroph adenomas in rats and humans, and highlighted common dysregulated genes, several of which were not previously implicated in pituitary tumorigenesis. Two such genes, CYP11A1 and NUSAP1, were analyzed in 39 human gonadotroph adenomas by qRT-PCR and found to be up-regulated in 77 and 95 % of cases, respectively. Immunohistochemistry detected high P450scc (encoded by CYP11A1) and NuSAP expression in 18 human gonado¬troph tumors. In vitro studies demonstrated for the first time that Cyp11a1 is a target of SF-1 in gonadotroph cells and promotes proliferation/survival of rat pituitary adenoma pri¬mary cells and cell lines. Our studies reveal clues about the molecular mechanisms driving rat and human gonadotroph adenomas development, and may help identify previously unexplored biomarkers for clinical use.
2013-07-10 | GSE23207 | GEO