The Experts below are selected from a list of 690996 Experts worldwide ranked by ideXlab platform
Daniel R Salomon - One of the best experts on this subject based on the ideXlab platform.
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a genome wide survey of mutations in the jurkat Cell Line
BMC Genomics, 2018Co-Authors: Louis Gioia, Azeem Siddique, Steven R Head, Daniel R SalomonAbstract:The Jurkat Cell Line has an extensive history as a model of T Cell signaling. But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the Cell Line paralleled normal human T Cells. While numerous expression deficiencies have been described in Jurkat, genetic explanations have only been provided for a handful of defects. Here, we report a comprehensive catolog of genomic variation in the Jurkat Cell Line based on whole-genome sequencing. With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects. We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the Cell Line. The Jurkat Cell Line harbors many mutations that are associated with cancer and contribute to Jurkat’s unique characteristics. Genes with damaging mutations in the Jurkat Cell Line are involved in T-Cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1). This work ties together decades of molecular experiments and serves as a resource that will streamLine both the interpretation of past research and the design of future Jurkat studies.
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a genome wide survey of mutations in the jurkat Cell Line
bioRxiv, 2017Co-Authors: Louis Gioia, Azeem Siddique, Steven R Head, Daniel R SalomonAbstract:The Jurkat Cell Line has an extensive history as a model of T Cell signaling. But at the turn of the 21st century, some irregularities were observed in Jurkat9s expression of central regulators of T Cell receptor signaling, which raised doubts about how closely the Cell Line paralleled normal human T Cells. While numerous expression deficiencies have been described in Jurkat, genetic explanations have only been provided for a handful of defects. Here, we report a comprehensive catolog of genomic variation in the Jurkat Cell Line based on whole-genome sequencing. With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects. We confirm the majority of documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the Cell Line. This work ties together decades of molecular experiments and serves as a resource that will streamLine both the interpretation of past research and the design of future Jurkat studies.
Nicholas J Clemons - One of the best experts on this subject based on the ideXlab platform.
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characterization of a novel tumorigenic esophageal adenocarcinoma Cell Line oanc1
Digestive Diseases and Sciences, 2014Co-Authors: Nicholas J Clemons, Christina M Fennell, Siddhartha Deb, Andrew Fellowes, Alexander Dobrovic, Wayne A PhillipsAbstract:Esophageal adenocarcinoma (EAC) has a very high case fatality rate and is one of the fastest rising cancers worldwide. At the same time, research into EAC has been hampered by a relative lack of pre-clinical models, including representative Cell Lines. The purpose of this study was to establish and characterize a new EAC Cell Line. Tumor Cells were isolated from EAC tissue by enzymatic digestion. Origin of the Cell Line was confirmed by microsatellite-based genotyping. A panel of cancer-related genes was screened for mutations by targeted deep sequencing, Sanger sequencing and high resolution melting. CDKN2A promoter methylation was assessed by methylation specific high resolution melting. HER2 amplification was assessed by fluorescent in situ hybridization. Immunohistochemistry was used to assess expression of markers in xenografts grown in SCID mice. A novel EAC Cell Line, OANC1, was derived from a Barrett’s-associated EAC. Microsatellite-based genotyping of OANC1 and patient DNA confirmed the origin of the Cell Line. Sequencing of OANC1 DNA identified homozygous TP53 missense (c.856G>A, p.E286K) and SMAD4 nonsense (c.1333C>T, p.R445X) mutations. OANC1 are tumorigenic when injected sub-cutaneously into SCID mice and xenografts were positive for columnar, glandular and intestinal epithelial markers commonly expressed in EAC. Xenografts exhibited strong p53 expression, consistent with a TP53 mutation. Some proteins, including p16, EGFR and β-catenin, had heterogeneous expression patterns across xenograft cross-sections, indicative of tumor heterogeneity. OANC1 represents a valuable addition to the limited range of pre-clinical models for EAC. This new Cell Line will be a useful model system for researchers studying both basic and translational aspects of this disease.
Anson W Lowe - One of the best experts on this subject based on the ideXlab platform.
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mistaken identity of widely used esophageal adenocarcinoma Cell Line te 7
Cancer Research, 2007Co-Authors: Jurjen J Boonstra, Albertina W Van Der Velden, Erwin C W Beerens, Ronald Van Marion, Yuiko Moritafujimura, Yasuhisa Matsui, Tetsuro Nishihira, Chris Tselepis, Pierre Hainaut, Anson W LoweAbstract:Cancer of the esophagus is the seventh leading cause of cancer death worldwide. Esophageal carcinoma Cell Lines are useful models to study the biological and genetic alterations in these tumors. An important prerequisite of Cell Line research is the authenticity of the used Cell Lines because the mistaken identity of a Cell Line may lead to invalid conclusions. Estimates indicate that up to 36% of the Cell Lines are of a different origin or species than supposed. The TE series, established in late 1970s and early 1980s by Nishihira et al. in Japan, is one of the first esophageal cancer Cell Line series that was used throughout the world. Fourteen TE Cell Lines were derived from human esophageal squamous Cell carcinomas and one, TE-7, was derived from a primary esophageal adenocarcinoma. In numerous studies, this TE-7 Cell Line was used as a model for esophageal adenocarcinoma because it is one of the few esophageal adenocarcinoma Cell Lines existing. We investigated the authenticity of the esophageal adenocarcinoma Cell Line TE-7 by xenografting, short tandem repeat profiling, mutation analyses, and array-comparative genomic hybridization and showed that Cell Line TE-7 shared the same genotype as the esophageal squamous Cell carcinoma Cell Lines TE-2, TE-3, TE-12, and TE-13. In addition, for more than a decade, independent TE-7 cultures from Japan, United States, United Kingdom, France, and the Netherlands had the same genotype. Examination of the TE-7 Cell Line xenograft revealed the histology of a squamous Cell carcinoma. We conclude that the TE-7 Cell Line, used in several laboratories throughout the world, is not an adenocarcinoma, but a squamous Cell carcinoma Cell Line. Furthermore, the Cell Lines TE-2, TE-3, TE-7, TE-12, and TE-13 should be regarded as one single squamous Cell carcinoma Cell Line.
F J Lopez - One of the best experts on this subject based on the ideXlab platform.
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Androgen responsiveness of the pituitary gonadotrope Cell Line LT2
2015Co-Authors: Mark A Lawson, C A Glidewell-kenney, F J LopezAbstract:Androgens have a profound effect on the hypothalamic– pituitary axis by reducing the synthesis and release of the pituitary gonadotropin LH. The effect on LH is partly a consequence of a direct, steroid-dependent action on pituitary function. Although androgen action has been well studied in vivo, in vitro Cell models of androgen action on pituitary gonadotropes have been scarce. Recently, an LH-expressing Cell Line, LT2, was generated by tumori-genesis targeted to the LH-producing Cells of the mouse pituitary. The purpose of these studies was to determine the presence of androgen receptor (AR) and establish its function in this Cell Line. RT-PCR analysis indicated that the LT2 Cell Line expresses AR mRNA. Transient transfection assays, using the mouse mammary tumor virus (MMTV) promoter, showed that a functional AR is also present. Testosterone (TEST), dihydrotestosterone (DHT), 7-methyl-19-nortestosterone (MENT), and fluoxymesterone (FLUOXY) increased reporter gene activity in the rank order of potencies MENT>DHT> TEST>FLUOXY. Additionally, activation of MMTV promoter activity by DHT in LT2 Cells was diminished by the AR antagonists casodex and 2-hydroxy-flutamide, indicating that the effects of DHT are mediated through AR. In summary, these studies showed that the LT2 Cell Line is a useful model for the evaluation and molecular characterization of androgen action in pituitary gonadotropes
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androgen responsiveness of the pituitary gonadotrope Cell Line lbetat2
Journal of Endocrinology, 2001Co-Authors: Mark A Lawson, Christine A Glidewellkenney, F J LopezAbstract:Androgens have a profound effect on the hypothalamic-pituitary axis by reducing the synthesis and release of the pituitary gonadotropin LH. The effect on LH is partly a consequence of a direct, steroid-dependent action on pituitary function. Although androgen action has been well studied in vivo, in vitro Cell models of androgen action on pituitary gonadotropes have been scarce. Recently, an LH-expressing Cell Line, LbetaT2, was generated by tumorigenesis targeted to the LH-producing Cells of the mouse pituitary. The purpose of these studies was to determine the presence of androgen receptor (AR) and establish its function in this Cell Line. RT-PCR analysis indicated that the LbetaT2 Cell Line expresses AR mRNA. Transient transfection assays, using the mouse mammary tumor virus (MMTV) promoter, showed that a functional AR is also present. Testosterone (TEST), dihydrotestosterone (DHT), 7alpha-methyl-19-nortestosterone (MENT), and fluoxymesterone (FLUOXY) increased reporter gene activity in the rank order of potencies MENT>DHT> TEST>FLUOXY. Additionally, activation of MMTV promoter activity by DHT in LbetaT2 Cells was diminished by the AR antagonists casodex and 2-hydroxy-flutamide, indicating that the effects of DHT are mediated through AR. In summary, these studies showed that the LbetaT2 Cell Line is a useful model for the evaluation and molecular characterization of androgen action in pituitary gonadotropes.
Louis Gioia - One of the best experts on this subject based on the ideXlab platform.
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a genome wide survey of mutations in the jurkat Cell Line
BMC Genomics, 2018Co-Authors: Louis Gioia, Azeem Siddique, Steven R Head, Daniel R SalomonAbstract:The Jurkat Cell Line has an extensive history as a model of T Cell signaling. But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the Cell Line paralleled normal human T Cells. While numerous expression deficiencies have been described in Jurkat, genetic explanations have only been provided for a handful of defects. Here, we report a comprehensive catolog of genomic variation in the Jurkat Cell Line based on whole-genome sequencing. With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects. We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the Cell Line. The Jurkat Cell Line harbors many mutations that are associated with cancer and contribute to Jurkat’s unique characteristics. Genes with damaging mutations in the Jurkat Cell Line are involved in T-Cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1). This work ties together decades of molecular experiments and serves as a resource that will streamLine both the interpretation of past research and the design of future Jurkat studies.
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a genome wide survey of mutations in the jurkat Cell Line
bioRxiv, 2017Co-Authors: Louis Gioia, Azeem Siddique, Steven R Head, Daniel R SalomonAbstract:The Jurkat Cell Line has an extensive history as a model of T Cell signaling. But at the turn of the 21st century, some irregularities were observed in Jurkat9s expression of central regulators of T Cell receptor signaling, which raised doubts about how closely the Cell Line paralleled normal human T Cells. While numerous expression deficiencies have been described in Jurkat, genetic explanations have only been provided for a handful of defects. Here, we report a comprehensive catolog of genomic variation in the Jurkat Cell Line based on whole-genome sequencing. With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects. We confirm the majority of documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the Cell Line. This work ties together decades of molecular experiments and serves as a resource that will streamLine both the interpretation of past research and the design of future Jurkat studies.
