Cell lines from MYCN transgenic murine tumours reflect the molecular and biological characteristics of human neuroblastoma.
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.
Cheng
Andy J
AJ
Children's Cancer Institute Australia for Medical Research, P.O. Box 81, Randwick, 2031 Sydney, Australia.
Cheng
Ngan Ching
NC
Ford
Jette
J
Smith
Janice
J
Murray
Jayne E
JE
Flemming
Claudia
C
Lastowska
Maria
M
Jackson
Michael S
MS
Hackett
Christopher S
CS
Weiss
William A
WA
Marshall
Glenn M
GM
Kees
Ursula R
UR
Norris
Murray D
MD
Haber
Michelle
M
D000818:Animals; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D015870:Gene Expression; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007621:Karyotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D000071447:N-Myc Proto-Oncogene Protein; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011003:Ploidies
C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins