The Experts below are selected from a list of 2652 Experts worldwide ranked by ideXlab platform
Peter W Andrews - One of the best experts on this subject based on the ideXlab platform.
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embryonic stem es cells and embryonal carcinoma ec cells opposite sides of the same coin
Biochemical Society Transactions, 2005Co-Authors: Peter W Andrews, Ivan Damjanov, Maryam Moghaddam Matin, Ahmad Reza Bahrami, Paul J Gokhale, Jonathan S DraperAbstract:Embryonal carcinoma (EC) cells are the stem cells of Teratocarcinomas, and the malignant counterparts of embryonic stem (ES) cells derived from the inner cell mass of blastocyst-stage embryos, whether human or mouse. On prolonged culture in vitro , human ES cells acquire karyotypic changes that are also seen in human EC cells. They also ‘adapt’, proliferating faster and becoming easier to maintain with time in culture. Furthermore, when cells from such an ‘adapted’ culture were inoculated into a SCID (severe combined immunodeficient) mouse, we obtained a Teratocarcinoma containing histologically recognizable stem cells, which grew out when the tumour was explanted into culture and exhibited properties of the starting ES cells. In these features, the ‘adapted’ ES cells resembled malignant EC cells. The results suggest that ES cells may develop in culture in ways that mimic changes occurring in EC cells during tumour progression.
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from Teratocarcinomas to embryonic stem cells
Philosophical Transactions of the Royal Society B, 2002Co-Authors: Peter W AndrewsAbstract:The recent derivation of human embryonic stem (ES) cell lines, together with results suggesting an unexpected degree of plasticity in later, seemingly more restricted, stem cells (so-called adult stem cells), have combined to focus attention on new opportunities for regenerative medicine, as well as for understanding basic aspects of embryonic development and diseases such as cancer. Many of the ideas that are now discussed have a long history and much has been underpinned by the earlier studies of Teratocarcinomas, and their embryonal carcinoma (EC) stem cells, which present a malignant surrogate for the normal stem cells of the early embryo. Nevertheless, although the potential of EC and ES cells to differentiate into a wide range of tissues is now well attested, little is understood of the key regulatory mechanisms that control their differentiation. Apart from the intrinsic biological interest in elucidating these mechanisms, a clear understanding of the molecular process involved will be essential if the clinical potential of these cells is to be realized. The recent observations of stem-cell plasticity suggest that perhaps our current concepts about the operation of cell regulatory pathways are inadequate, and that new approaches for analysing complex regulatory networks will be essential.
Qijun Qian - One of the best experts on this subject based on the ideXlab platform.
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establishment of mouse Teratocarcinomas stem cells line and screening genes responsible for malignancy
PLOS ONE, 2012Co-Authors: Tao Liu, Ying Wang, Xinrong Peng, Liqing Zhang, Qijun Qian, Jingbo Cheng, Huajun JinAbstract:The sequential transplantation of embryonal carcinoma cells in vivo can accelerate the growth and malignancy of Teratocarcinomas. However, the possible molecular mechanisms in this process that reflect cancer formation in the early stage are largely unknown and. To identify which genes are associated with the changes of malignancy of Teratocarcinomas, we established a tumorigenesis model in which Teratocarcinoma were induced via injecting embryonic stem cells into immuno-deficiency mice, isolating Teratocarcinoma stem cell from a Teratocarcinoma in serum-free culture medium and injecting Teratocarcinoma stem cells into immune-deficient mice continuously. By using high-throughput deep sequence technology, we identified 26 differentially expressed genes related to the changes of characteristics of Teratocarcinoma stem cell in which 18 out of 26 genes were down-regulated and 8 genes were up-regulated. Among these genes, several tumor-related genes such as Gata3, Arnt and Tdgf1, epigenetic associated genes such as PHC1 and Uty were identified. Pathway enrichment analysis result revealed that Wnt signaling pathway, primary immunodeficiency pathway, antigen processing and presentation pathway and allograft rejection pathway were involved in the Teratocarcinoma tumorigenesis (corrected p value<0.05). In summary, our study established a tumorigenesis model and proposed some candidate genes and signaling pathways that may play a key role in the early stage of cancer occurrence.
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Establishment of Mouse Teratocarcinomas Stem Cells Line and Screening Genes Responsible for Malignancy
2012Co-Authors: Tao Liu, Ying Wang, Xinrong Peng, Liqing Zhang, Jingbo Cheng, Huajun Jin, Qijun QianAbstract:The sequential transplantation of embryonal carcinoma cells in vivo can accelerate the growth and malignancy of Teratocarcinomas. However, the possible molecular mechanisms in this process that reflect cancer formation in the early stage are largely unknown and. To identify which genes are associated with the changes of malignancy of Teratocarcinomas, we established a tumorigenesis model in which Teratocarcinoma were induced via injecting embryonic stem cells into immuno-deficiency mice, isolating Teratocarcinoma stem cell from a Teratocarcinoma in serum-free culture medium and injecting Teratocarcinoma stem cells into immune-deficient mice continuously. By using high-throughput deep sequence technology, we identified 26 differentially expressed genes related to the changes of characteristics of Teratocarcinoma stem cell in which 18 out of 26 genes were down-regulated and 8 genes were up-regulated. Among these genes, several tumor-related genes such as Gata3, Arnt and Tdgf1, epigenetic associated genes such as PHC1 and Uty were identified. Pathway enrichment analysis result revealed that Wnt signaling pathway, primary immunodeficiency pathway, antigen processing and presentation pathway and allograft rejection pathway were involved in the Teratocarcinoma tumorigenesis (corrected p value,0.05). In summary, our study established a tumorigenesis model and proposed some candidate gene
Maxine F Singer - One of the best experts on this subject based on the ideXlab platform.
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sequence specific single strand rna binding protein encoded by the human line 1 retrotransposon
The EMBO Journal, 1997Co-Authors: Hirohiko Hohjoh, Maxine F SingerAbstract:Previous experiments using human Teratocarcinoma cells indicated that p40, the protein encoded by the first open reading frame (ORF) of the human LINE-1 (L1Hs) retrotransposon, occurs in a large cytoplasmic ribonucleoprotein complex in direct association with L1Hs RNA(s), the p40 RNP complex. We have now investigated the interaction between partially purified p40 and L1Hs RNA in vitro using an RNA binding assay dependent on co-immunoprecipitation of p40 and bound RNA. These experiments identified two p40 binding sites on the full-length sense strand L1Hs RNA. Both sites are in the second ORF of the 6000 nt RNA: site A between residues 1999 and 2039 and site B between residues 4839 and 4875. The two RNA segments share homologous regions. Experiments involving UV cross-linking followed by immunoprecipitation indicate that p40 in the in vitro complex is directly associated with L1Hs RNA, as it is in the p40 RNP complex found in Teratocarcinoma cells. Binding and competition experiments demonstrate that p40 binds to single-stranded RNA containing a p40 binding site, but not to single-stranded or double-stranded DNA, double-stranded RNA or a DNA-RNA hybrid containing a binding site sequence. Thus, p40 appears to be a sequence-specific, single-strand RNA binding protein.
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studies on p40 the leucine zipper motif containing protein encoded by the first open reading frame of an active human line 1 transposable element
Journal of Biological Chemistry, 1992Co-Authors: S E Holmes, Maxine F Singer, G D SwergoldAbstract:Abstract Full-length human LINE-1 retrotransposons encode p40 proteins with varying electrophoretic mobilities under denaturing conditions. The p40 expressed from the first open reading frame in the LINE-1 copy designated L1.2A co-electrophoreses with the endogenous p40 in human Teratocarcinoma cells. This finding is consistent with previous data indicating that L1.2A is an active element. The amino acid sequence in the central region of the L1.2A p40 accounts, at least in part, for its characteristic mobility. This region includes sequences which can, in principle, form a leucine zipper.
Reinhard Kurth - One of the best experts on this subject based on the ideXlab platform.
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expression of human endogenous retrovirus k in melanomas and melanoma cell lines
Cancer Research, 2005Co-Authors: Kristina Buscher, Maja A Hofmann, Wolfram Sterry, Reinhard Kurth, Uwe Trefzer, Joachim DennerAbstract:The human endogenous retrovirus K family (HERV-K) comprises 30 to 50 closely related proviruses, most of which are defective. In contrast to all other human endogenous retroviruses, some HERV-K proviruses have maintained open reading frames for all viral proteins. In addition to the structural proteins Gag and Env and the reverse transcriptase, two regulatory proteins (Rec and Np9) have been described. Malignant melanoma has the highest mortality among skin cancers and is particularly aggressive. To study the expression of HERV-K, a set of seven primers was developed that allows discrimination between full-length and spliced mRNA and mRNA from deleted and undeleted proviruses. Expression of full-length mRNA from deleted and undeleted proviruses was detected in all human cells investigated. Expression of spliced env and rec was detected in a Teratocarcinoma cell line, in 45% of the metastatic melanoma biopsies, and in 44% of the melanoma cell lines. In normal neonatal melanocytes, spliced rec was detected but not spliced env. Viral proteins were shown to be expressed in primary melanomas, metastases, and melanoma cell lines by immunohistochemistry, immunofluorescence, and Western blot analyses using specific antisera. For the first time, antibodies against HERV-K were found in melanoma patients. Melanomas are, in addition to Teratocarcinomas and human breast cancer, the third tumor type with enhanced expression of HERV-K.
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identification of human endogenous retroviruses with complex mrna expression and particle formation
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Roswitha Lower, Klaus Boller, Brigitte Hasenmaier, Christine Korbmacher, Nikolaus Mullerlantzsch, Johannes Lower, Reinhard KurthAbstract:Abstract Retroviruses comprise strains with considerable disease potential in animals and humans. In addition to exogenous strains transmitted horizontally, endogenous proviruses are transmitted through the germ line. Some of these endogenous retroviruses can be pathogenic in mice and possibly in other animal species. They may also be considered as mobile genetic elements with the potential to produce mutations. In humans, genomic DNA contains numerous endogenous retroviral sequences detected by their partial relatedness to animal retroviruses. However, all proviruses sequenced so far have been found to be defective. In this communication, we describe the expression of a family of human endogenous retrovirus sequences (HERV-K) in GH cells, a Teratocarcinoma cell line producing the human Teratocarcinoma-derived retrovirus (HTDV) particles previously described by us. Four viral mRNA species could be identified, including a full-length mRNA. The other three subgenomic mRNAs are generated by single or double splicing events. This expression pattern is reminiscent of the more complex control of virus gene regulation observed, for example, with lenti- or spumavirus strains, although HERV-K shows no sequence homology to human T-lymphotropic virus or human immunodeficiency virus. Sequence analysis of expressed HERV-K genomes revealed non-defective gag genes, a prerequisite for particle formation. Open reading frames were also observed in pol and env. Antisera raised against recombinant gag proteins of HERV-K stained HTDV particles in immunoelectron microscopy, linking them to the HERV-K family.
Johannes Lower - One of the best experts on this subject based on the ideXlab platform.
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expression of the human endogenous retrovirus htdv herv k is enhanced by cellular transcription factor yy1
Journal of Virology, 1999Co-Authors: Michael Knössl, Roswitha Lower, Johannes LowerAbstract:The human endogenous retrovirus HTDV/HERV-K, which resides in moderate copy numbers in the human genome, is expressed in a cell-type-specific manner, predominantly in Teratocarcinoma cells. We have analyzed the regulatory potential of the 5' enhancer of the HERV-K long terminal repeat. Protein extracts of HERV-K-expressing Teratocarcinoma cell lines (GH and Tera2) and nonexpressing HeLa and HepG2 cells form different protein complexes on the enhancer sequence as detected by electrophoretic mobility shift assays (EMSA). Using competition EMSAs, DNase I footprinting, and supershift experiments, we localized the binding site of these complexes to a 20-bp sequence within the enhancer and showed that the transcription factor YY1 is one component of the HERV-K enhancer complex. Replacement of the YY1 binding site with unrelated sequences reduced expression of the luciferase gene as a reporter in transient-transfection assays.
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identification of human endogenous retroviruses with complex mrna expression and particle formation
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Roswitha Lower, Klaus Boller, Brigitte Hasenmaier, Christine Korbmacher, Nikolaus Mullerlantzsch, Johannes Lower, Reinhard KurthAbstract:Abstract Retroviruses comprise strains with considerable disease potential in animals and humans. In addition to exogenous strains transmitted horizontally, endogenous proviruses are transmitted through the germ line. Some of these endogenous retroviruses can be pathogenic in mice and possibly in other animal species. They may also be considered as mobile genetic elements with the potential to produce mutations. In humans, genomic DNA contains numerous endogenous retroviral sequences detected by their partial relatedness to animal retroviruses. However, all proviruses sequenced so far have been found to be defective. In this communication, we describe the expression of a family of human endogenous retrovirus sequences (HERV-K) in GH cells, a Teratocarcinoma cell line producing the human Teratocarcinoma-derived retrovirus (HTDV) particles previously described by us. Four viral mRNA species could be identified, including a full-length mRNA. The other three subgenomic mRNAs are generated by single or double splicing events. This expression pattern is reminiscent of the more complex control of virus gene regulation observed, for example, with lenti- or spumavirus strains, although HERV-K shows no sequence homology to human T-lymphotropic virus or human immunodeficiency virus. Sequence analysis of expressed HERV-K genomes revealed non-defective gag genes, a prerequisite for particle formation. Open reading frames were also observed in pol and env. Antisera raised against recombinant gag proteins of HERV-K stained HTDV particles in immunoelectron microscopy, linking them to the HERV-K family.
