Physical and functional characterization of the human LGI1 gene and its possible role in glioma development

被引:0
|
作者
Dietmar Krex
Martin Hauses
Hella Appelt
Brigitte Mohr
Gerhard Ehninger
Hans Schackert
Gabriele Schackert
机构
[1] Department of Neurosurgery,
[2] Universitätsklinikum Carl Gustav Carus,undefined
[3] University of Technology,undefined
[4] Dresden,undefined
[5] Fetscherstrasse 74,undefined
[6] 01307 Dresden,undefined
[7] Department of Internal Medicine/Hematology and Oncology,undefined
[8] Universitätsklinikum Carl Gustav Carus,undefined
[9] University of Technology,undefined
[10] Dresden,undefined
[11] Department of Surgical Research,undefined
[12] Universitätsklinikum Carl Gustav Carus,undefined
[13] University of Technology,undefined
[14] Dresden,undefined
来源
Acta Neuropathologica | 2002年 / 103卷
关键词
LGI1 Glioblastoma Pathogenesis Tumor suppressor Gene;
D O I
暂无
中图分类号
学科分类号
摘要
The human gene termed LGI1 (leucine-rich gene – glioma inactivated) has been isolated recently, and is supposed to be an additional candidate tumor suppressor gene involved in the formation and progression of glioblastoma multiforme [Chernova et al. (1998) Oncogene 17:2873–2881]. To test this hypothesis and to complete the characterization of the gene, we performed various detailed studies on the genomic structure, the mRNA expression level, the integrity of the cDNA, and retroviral gene transfer into LGI1-deficient cell lines. Two single nucleotide polymorphisms in the promotor region and a highly polymorphic intragenic microsatellite repeat between exon 4 and 5 were found. Phylogenetic sequence analysis techniques were applied, which showed functional relationships between LGI1 and TRK and SLIT protein families that are known to be involved in development and maintenance of the nervous system. Fluorescence in situ hybridization (FISH) analysis showed LGI1 to be present on 10q24 in each of 11 glioma-derived cell lines evaluated. Sequence analysis of the LGI1 transcript did not detect any mutation. Relative amounts of LGI1 mRNA copy numbers as measured by the real-time fluorescence detection LightCycler technology differed more than three orders of magnitude and were significantly reduced in 10 of 11 cell lines. Retroviral gene transfer into LGI1-deficient glioma-derived cell lines could not substantiate any difference to control infected cultures regarding growth rate, S phase transition, and maintenance of marker gene expression. The strong homology to proteins involved in development, differentiation, or maintenance of the nervous system provides evidence for a function of the LGI1 protein in neural tissue. The observation that translocation or deletion of the LGI1 locus or mutation of the coding sequence of the LGI1 mRNA is not a frequent event in malignant glioma cell lines suggests that epigenetic factors lead to substantial differences in the amount of LGI1 mRNA expression. In addition, that the effect is lacking after retroviral gene transfer in cell culture suggests that binding of some kind of a ligand is essential for its biological activity.
引用
收藏
页码:255 / 266
页数:11
相关论文
共 50 条
  • [1] Physical and functional characterization of the human LGI1 gene and its possible role in glioma development
    Krex, D
    Hauses, M
    Appelt, H
    Mohr, B
    Ehninger, G
    Schackert, HK
    Schackert, G
    ACTA NEUROPATHOLOGICA, 2002, 103 (03) : 255 - 266
  • [2] LGI1:: a gene involved in epileptogenesis and glioma progression?
    Gu, W
    Brodtkorb, E
    Piepoli, T
    Finocchiaro, G
    Steinlein, OK
    NEUROGENETICS, 2005, 6 (02) : 59 - 66
  • [3] LGI1: a gene involved in epileptogenesis and glioma progression?
    W. Gu
    E. Brodtkorb
    T. Piepoli
    G. Finocchiaro
    O. K. Steinlein
    Neurogenetics, 2005, 6 : 59 - 66
  • [4] Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene
    Kunapuli, P
    Chitta, KS
    Cowell, JK
    ONCOGENE, 2003, 22 (26) : 3985 - 3991
  • [5] Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene
    Padmaja Kunapuli
    Kasyapa S Chitta
    John K Cowell
    Oncogene, 2003, 22 : 3985 - 3991
  • [6] Expression Profile of Lgi1 Gene in Mouse Brain During Development
    Patrícia A. O. Ribeiro
    Lourenço Sbragia
    Rovilson Gilioli
    Francesco Langone
    Fábio F. Conte
    Iscia Lopes-Cendes
    Journal of Molecular Neuroscience, 2008, 35 : 323 - 329
  • [7] Expression profile of Lgi1 gene in mouse brain during development
    Ribeiro, Patricia A. O.
    Sbragia, Lourenco
    Gilioli, Rovilson
    Langone, Francesco
    Conte, Fabio F.
    Lopes-Cendes, Iscia
    JOURNAL OF MOLECULAR NEUROSCIENCE, 2008, 35 (03) : 323 - 329
  • [8] Mutation analysis of the leucine-rich, glioma inactivated 1 gene (LGI1) in Japanese febrile seizure patients
    Nakayama, J
    Hamano, K
    Iwasaki, N
    Ohta, M
    Nakahara, S
    Matsui, A
    Arinami, T
    NEUROPEDIATRICS, 2003, 34 (05) : 234 - 236
  • [9] The LGI1/Epitempin gene encodes two protein isoforms differentially expressed in human brain
    Furlan, Sandra
    Roncaroli, Federico
    Forner, Francesca
    Vitiello, Libero
    Calabria, Elisa
    Piquer-Sirerol, Salome
    Valle, Giorgio
    Perez-Tur, Jordi
    Michelucci, Roberto
    Nobile, Carlo
    JOURNAL OF NEUROCHEMISTRY, 2006, 98 (03) : 985 - 991
  • [10] The temporal and spatial expression pattern of the LGI1 epilepsy predisposition gene during mouse embryonic cranial development
    Silva, Jeane
    Wang, Guanghu
    Cowell, John K.
    BMC NEUROSCIENCE, 2011, 12