Journal
EUROPEAN JOURNAL OF CANCER
Volume 43, Issue 9, Pages 1467-1475Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2007.03.008
Keywords
neuroblastoma; MYCN oncogene; transgenic mice; murine cell lines
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Funding
- NCI NIH HHS [R01 CA102321-08, R01 CA102321, R01 CA102321-06, R01 CA102321-07, R01 CA102321-04A1, R01 CA102321-05] Funding Source: Medline
- NINDS NIH HHS [R01 NS055750-01A2S1, R01 NS055750-02S1, K02 NS002226, R01 NS055750-04, R01 NS055750-01A2, K02NS02226-05, R01 NS055750-03, R01 NS055750, R01 NS055750-02] Funding Source: Medline
- PHS HHS [R01CAA102321] Funding Source: Medline
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Overexpression. of the human MYCN oncogene driven by a tyrosine hydroxylase promoter causes tumours in transgenic mice that recapitulate the childhood cancer neuroblastoma. To establish an in vitro model to study this process, a series of isogenic cell lines were developed from these MYCN-driven murine tumours. Lines were established from tumours arising in homozygous and hemizygous MYCN transgenic mice. Hemizygous tumours gave rise to cell lines growing only in suspension. Homozygous tumours gave rise to similar suspension lines as well as morphologically distinct substrate-adherent lines characteristic of human S-type neuroblastoma cells. FISH analysis demonstrated selective MYCN transgene amplification in cell lines derived from hemizygous mice. Comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH) analysis confirmed a range of neuroblastoma-associated genetic changes in the various lines, in particular, gain of regions syntenic with human 17q. These isogenic lines together with the transgenic mice thus represent valuable models for investigating the biological characteristics of aggressive neuroblastoma. (C) 2007 Elsevier Ltd. All rights reserved.
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