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Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene. 总被引:26,自引:2,他引:24 下载免费PDF全文
S E Bodrug B J Warner M L Bath G J Lindeman A W Harris J M Adams 《The EMBO journal》1994,13(9):2124-2130
Cyclin D1 is the regulatory subunit of certain protein kinases thought to advance the G1 phase of the cell cycle. Deregulated cyclin D1 expression has been implicated in several human neoplasms, most consistently in centrocytic B lymphoma, where the cyclin D1 gene usually has been translocated to an immunoglobulin locus. To determine directly whether constitutive cyclin D1 expression is lymphomagenic, transgenic mice were generated having the cyclin D1 gene linked to an immunoglobulin enhancer. Despite abundant transgene expression, their lymphocytes were normal in cell cycle activity, size and mitogen responsiveness, but young transgenic animals contained fewer mature B- and T-cells. Although spontaneous tumours were infrequent, lymphomagenesis was much more rapid in mice that co-expressed the cyclin D1 transgene and a myc transgene than in mice expressing either transgene alone. Moreover, the spontaneous lymphomas of myc transgenic animals often ectopically expressed the endogenous cyclin D1 gene. These findings indicate that this G1 cyclin can modulate differentiation and collaborate with myc-like genes in oncogenesis. 相似文献
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A Ma R K Smith A Tesfaye P Achacoso R Dildrop N Rosenberg F W Alt 《Molecular and cellular biology》1991,11(1):440-444
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N-myc transgene promotes B lymphoid proliferation, elicits lymphomas and reveals cross-regulation with c-myc. 总被引:12,自引:6,他引:12 下载免费PDF全文
To assess the impact of constitutive N-myc expression on lymphocytes, we generated lines of transgenic mice bearing the murine N-myc oncogene coupled to the immunoglobulin heavy chain enhancer (E mu). As in mice carrying an analogous c-myc construct, E mu-N-myc mice exhibit a limited overgrowth of cycling pre-B cells and eventually succumb to clonal B lymphoid tumours. The endogenous N-myc and c-myc alleles are silent in both E mu-N-myc and E mu-myc lymphomas, suggesting that these genes are subject to auto- and cross-regulation. The regulatory interaction and the similar biological effects of N-myc and c-myc imply that the two genes perform interchangeable functions in the promotion of cell proliferation. 相似文献
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C Birchmeier D Birnbaum G Waitches O Fasano M Wigler 《Molecular and cellular biology》1986,6(9):3109-3116
A human oncogene, mcf3, previously detected by a combination of DNA-mediated gene transfer and a tumorigenicity assay, derives from a human homology of the avian v-ros oncogene. Both v-ros and mcf3 can encode a protein with homology to tyrosine-specific protein kinases, and both mcf3 and v-ros encode a potential transmembrane domain N terminal to the kinase domain. mcf3 probably arose during gene transfer from a normal human ros gene by the loss of a putative extracellular domain. There do not appear to be any other gross rearrangements in the structure of mcf3. 相似文献
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Telomeres, telomerase, and myc. An update 总被引:16,自引:0,他引:16
Cerni C 《Mutation research》2000,462(1):31-47
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Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice 总被引:41,自引:0,他引:41
To search for genes that can collaborate with myc in lymphomagenesis, we exploited retroviral insertional mutagenesis in E mu-myc transgenic mice. Moloney murine leukemia virus accelerated development of B lymphoid tumors. Three quarters contained a provirus within the known pim-1 or pim-2 loci, new loci bmi-1 and emi-1, or combinations of these. bmi-1 insertions predominated, occurring in half the tumors, and resulted in elevated bmi-1 mRNA levels. Significantly, the bmi-1 gene, which is expressed in diverse normal cells, encodes a Cys/His metal-binding motif (C3HC4) that resembles those in several DNA-binding proteins and defines a new category of zinc finger gene. Thus, myc-induced lymphomagenesis can entail the concerted action of several genes, including the presumptive nuclear regulator bmi-1. 相似文献
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《Cell》2022,185(17):3263-3277.e15
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Ming Ma Kai Zhao Wenting Wu Ruilin Sun Jian Fei 《Development, growth & differentiation》2014,56(2):152-160
N‐myc belongs to the Myc oncogene family and plays an essential role in mammalian embryonic development. The expression of N‐myc is dynamically regulated during embryonic development; however, its expression pattern has not been well characterized due to the lack of a suitable animal model. In this paper, a genetically modified mouse model was generated in which the enhanced green fluorescent protein (EGFP) coding sequence was inserted into the N‐myc locus, so that endogenous N‐myc expression could be traced by the signal of EGFP. The EGFP signal in the transgenic mouse was confirmed to be consistent with the expression pattern of endogenous N‐myc by fluorescence microscopy and immunohistochemical staining. Furthermore, the spatial and temporal expression of EGFP was observed in the central and peripheral nervous system, heart, lung and kidney, given the known indispensable role of N‐myc in their formation. EGFP was also strongly detected in the liver, paranephros and the epithelium of the intestine. The EGFP signal can be used to trace N‐myc expression in this transgenic mouse model. N‐myc expression was observed in specific locations and cell lineages, and dynamically changed during embryonic development. The changing N‐myc expression pattern seen in mouse embryonic development and the animal model described in this paper provide important insights and a new tool to research N‐myc function. 相似文献
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Molecular cloning and characterization of an activated human c-raf-1 gene. 总被引:6,自引:2,他引:4 下载免费PDF全文
M Fukui T Yamamoto S Kawai F Mitsunobu K Toyoshima 《Molecular and cellular biology》1987,7(5):1776-1781
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Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2 总被引:29,自引:0,他引:29
Murakami M Naraba H Tanioka T Semmyo N Nakatani Y Kojima F Ikeda T Fueki M Ueno A Oh S Kudo I 《The Journal of biological chemistry》2000,275(42):32783-32792
Here we report the molecular identification of membrane-bound glutathione (GSH)-dependent prostaglandin (PG) E(2) synthase (mPGES), a terminal enzyme of the cyclooxygenase (COX)-2-mediated PGE(2) biosynthetic pathway. The activity of mPGES was increased markedly in macrophages and osteoblasts following proinflammatory stimuli. cDNA for mouse and rat mPGESs encoded functional proteins that showed high homology with the human ortholog (microsomal glutathione S-transferase-like 1). mPGES expression was markedly induced by proinflammatory stimuli in various tissues and cells and was down-regulated by dexamethasone, accompanied by changes in COX-2 expression and delayed PGE(2) generation. Arg(110), a residue well conserved in the microsomal GSH S-transferase family, was essential for catalytic function. mPGES was functionally coupled with COX-2 in marked preference to COX-1, particularly when the supply of arachidonic acid was limited. Increased supply of arachidonic acid by explosive activation of cytosolic phospholipase A(2) allowed mPGES to be coupled with COX-1. mPGES colocalized with both COX isozymes in the perinuclear envelope. Moreover, cells stably cotransfected with COX-2 and mPGES grew faster, were highly aggregated, and exhibited aberrant morphology. Thus, COX-2 and mPGES are essential components for delayed PGE(2) biosynthesis, which may be linked to inflammation, fever, osteogenesis, and even cancer. 相似文献
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Cloning of E. coli pnp gene from an episome 总被引:13,自引:0,他引:13
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Direct evidence for intrastrand DNA inversion of kappa immunoglobulin gene segments in two murine plasmacytomas. 下载免费PDF全文
The products of kappa immunoglobulin gene recombination have been characterized in two murine plasmacytomas to examine the relationship between V-J products and reciprocal elements. By cloning, sequencing, hybridization, and application of the polymerase chain reaction, we have established the direct relationship of the kappa recombination products in these cells. The results provide stronger support for the intrastrand mechanism of kappa gene recombination as well as demonstrating a role for secondary, corrective recombinations. 相似文献