Rat model of the human "Triton" tumor: direct genetic evidence for the myogenic differentiation capacity of schwannoma cells using the mutant neu gene as a cell lineage marker.
Spontaneous myogenic differentiation was observed in 2 out of 15 cases when cells from schwannomas induced in the offspring of BDIX rats by transplacental exposure to N-ethyl-N-nitrosourea (EtNU) were grown in monolayer culture following fluorescence-activated cell sorting with monoclonal antibody (Mab) 217c. Myotubes and numerous mononucleated cells no longer expressed the Schwann cell antigens 217c and S-100 protein, but rather revealed the presence of desmin, the alpha-sarcomeric form (alpha-sr) of actin, and the cell surface antigen specified by Mab RB21-7, a 250 kD glycoprotein sharing an epitope with the neural cell adhesion molecule (N-CAM). Subcutaneous reimplantation of such cells into syngeneic animals led to the appearance of tumors composed of both S-100 positive Schwann cells and desmin and alpha-sr-actin positive rhabdomyoblasts, thus closely resembling the human "Triton" tumor. With the use of the polymerase chain reaction and allele-specific oligonucleotide hybridization, DNA isolated from individual myotubes was analyzed for the presence of a T----A transversion mutation at nucleotide 2012 of the neu gene, which is diagnostic of EtNU-induced rat schwannomas. All of the amplified DNA isolates contained the mutant neu allele, thus providing direct genetic proof for the capacity of mammalian neuroectodermal cells for myogenic differentiation.
Institute of Cell Biology (Cancer Research), West German Cancer Center Essen, University of Essen Medical School.
Nikitin AYu
K
K
Lennartz
K M
KM
Pozharisski
M F
MF
Rajewsky
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D007150:Immunohistochemistry; D009132:Muscles / Q000166:cytology*; D009154:Mutation; D009368:Neoplasm Transplantation; D009442:Neurilemmoma / Q000139:chemically induced / Q000473:pathology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D051381:Rats; D011919:Rats, Inbred Strains; D018719:Erb-b2 Receptor Tyrosine Kinases
D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases