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Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene

Oncogene volume 22, pages 3985–3991 (2003)Cite this article

Abstract

The leucine-rich, glioma-inactivated (LGI1) gene, located in 10q24, was originally identified because it was interrupted and inactivated by a reciprocal chromosome translocation in the T98G glioma cell line. Loss of LGI1 expression in high-grade brain tumors is correlated with the frequent loss of chromosome 10 during progression of gliomas. To investigate whether this gene can suppress the malignant phenotype in glioma cells, we introduced the LGI1 gene into cells that do (U87) and do not (T98G and A172) express LGI1 endogenously. A172 and T98G cells showed a significant reduction in cell proliferation potential as a result of re-expression of LGI1, whereas U87 cells did not. Using BD matrigel matrix chamber assays we were also able to show that the migration ability of the reconstituted A172 and T98G cells was also reduced considerably. Finally, these reconstituted T98G and A172 cells showed a significant reduction in the ability to form colonies in soft agar compared with the parental cells. This analysis clearly demonstrates that re-expression of the LGI1 gene in glioma cells that were null for its activity can greatly reduce their malignant potential. These observations provide the opportunity to investigate the role of LGI1 in gliomagenesis and, since LGI1 is predicted to be a membrane-bound protein, potentially provides the opportunity to develop novel treatment strategies for malignant gliomas.

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References

  • Albarosa R, Colombo BM, Roz L, Magnani I, Pollo B, Cirenei N, Giani C, Conti AM, Dinoato S and Finocchiaro G . (1996). Am. J. Hum. Genet., 58, 1260–1267.

  • Buchanan SG and Gay NJ . (1996). Prog. Biophys. Mol. Biol., 65, 1–44.

  • Chernova OB, Hunyadi A, Malaj E, Pan H, Crooks C, Roe B and Cowell JK . (2001). Oncogene, 20, 5378–5392.

  • Chernova O, Somerville RPT and Cowell JK . (1998). Oncogene, 17, 2873–2881.

  • Fults D, Brockmeyer D, Tullouis MW, Pedone CA and Cawthon RM . (1992). Cancer Res., 52, 674–679.

  • Fults D and Pedone C . (1993). Genes, Chromosomes Cancer, 7, 173–177.

  • Fults D, Pedone CA, Thomas GA and White R . (1990). Cancer Res., 50, 5784–5789.

  • Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H and Parks WP . (1973). J. Natl. Acad. Sci., 51, 1417–1423.

  • Jacobs JR . (2000). Prog. Neurobiol., 62, 475–508.

  • James CD, Carlbom E, Dumanski JP, Hansen M, Nordenskjold M, Collins VP and Cavenee WK . (1988). Cancer Res., 48, 5546–5551.

  • Karlbom AE, James CD, Boethius J, Cavenee WK, Collins VP, Nordenskjold M and Larsson C . (1993). Hum. Genet., 92, 169–174.

  • Kleihues P and Cavenee WK. (Eds) (2000). Pathology and Genetics of Tumors of the Nervous System. IARC Press: Lyon, France.

    Google Scholar 

  • Krex D, Hauses M, Appelt H, Mohr B, Ehninger G, Schackert KH and Scahkert G . (2002). Acta Neuropathol., 103, 255–266.

  • Li D and Sun H . (1997). Cancer Res., 57, 2124–2129.

  • Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler M and Parsons R . (1997). Science, 275, 1943–1947.

  • Mollenhauer J, Wiemann S, Scheurlen W, Korn B, Hayashi Y, Wilgenbus KK, von Deimling A and Poustka A . (1997). Nat. Genet., 17, 32–39.

  • Myers PM, Stolarov JP, Eng C, Li J, Wang SI, Wigler MH, Parsons R and Ronks NK . (1997). Proc. Natl. Acad. Sci. USA, 94, 9502–9057.

  • Papazisis KT, Geromichalos GD, Dimitriadis KA and Kortsaris AH . (1997). J. Immunol. Methods, 208, 151–158.

  • Pershouse MA, Stubblefield E, Hadim A, Killary AM, Yung WK and Steck PA . (1993). Cancer Res., 53, 5043–5050.

  • Ponten J and Macintyre EH . (1968). Acta Pathol. Microbiol. Scand., 74, 465–468.

  • Ransom DT, Ritland SR, Moertel CA, Dahl RJ, O'Fallon JR, Scheithauer BW, Kimmel DW, Kelly PJ, Olopade OI and Diaz Mo . (1992). Genes, Chromosomes Cancer, 5, 357–374.

  • Rasheed BK, Fuller GN, Friedman AH, Bigner DD and Bigner SH . (1992). Genes, Chromosomes Cancer, 5, 75–82.

  • Rasheed BKA, Atenzel TT, McLendon RE, Parson R, Friedman AH, Friedman HS, Bigner DD and Bigner SH . (1997). Cancer Res., 57, 4187–4190.

  • Sasaki H, Betensky RA, Cairncross JG and Louis DN . (2002). Cancer Res., 62, 1790–1796.

  • Steck PA, Ligon AH, Cheong P, Yung WK and Pershouse MA . (1995). Genes, Chromosomes Cancer, 12, 255–261.

  • Steck PA, Pershouse MA, Jasser SA, Yung WKA, Lin H, Lignon AH, Langford LA, Baumgard ML, Hatier T, Davies T, Frye C, Swedlund B, Teng DHF and Tavtigian SW . (1997). Nat. Genet., 15, 356–362.

  • Stein GH . (1979). J. Cell Physiol., 99, 43–54.

  • Still IH, Hamilton M, Vince P, Wolfman A and Cowell JK . (1999). Oncogene, 18, 4032–4038.

  • Somerville RPT, Chernova O, Liu S, Shoshan Y and Cowell JK . (2000). Mamm. Genome, 11, 622–627.

  • Somerville RPT, Shoshan Y, Eng C, Barnett G, Miller D and Cowell JK . (1998). Oncogene, 17, 1755–1757.

  • Wang SI, Puc J, Li B, Bruce JN, Ciarns P, Sidransky D and Parsons R . (1997). Cancer Res., 57, 4183–4186.

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  1. Department of Cancer Genetics, Roswell Park Cancer Institute, New York, Buffalo, 14263, NY, USA

    Padmaja Kunapuli, Kasyapa S Chitta & John K Cowell

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  1. Padmaja Kunapuli
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  2. Kasyapa S Chitta
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  3. John K Cowell
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Correspondence to John K Cowell.

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Kunapuli, P., Chitta, K. & Cowell, J. Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene. Oncogene 22, 3985–3991 (2003). https://doi.org/10.1038/sj.onc.1206584

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