Mouse tumor model for neurofibromatosis type 1

Science

Volumn 286, Issue 5447, 1999, Pages 2176-2179

  Vogel, Kristine S ^a,c   Klesse, Laura J ^a   Velasco Miguel, Susana ^a   Meyers, Kimberly ^a   Rushing, Elizabeth J ^b   Parada, Luis F ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c LOUISIANA STATE UNIV MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN P53;

ARTICLE; AUTOSOMAL DOMINANT DISORDER; DISEASE TRANSMISSION; GENE ACTIVATION; HETEROZYGOSITY LOSS; MALIGNANT TRANSFORMATION; NEURAL CREST; NEUROFIBROMATOSIS; ONCOGENE RAS; PHENOTYPE; PRIORITY JOURNAL; PROTO ONCOGENE;

ANIMALS; CELL DIFFERENTIATION; CELL TRANSFORMATION, NEOPLASTIC; CROSSES, GENETIC; DISEASE MODELS, ANIMAL; FEMALE; GENES, NEUROFIBROMATOSIS 1; GENES, P53; HETEROZYGOTE; HUMANS; LOSS OF HETEROZYGOSITY; MALE; MICE; MICE, INBRED C57BL; MUTATION; NEURAL CREST; NEUROFIBROMATOSIS 1; SARCOMA; SCHWANN CELLS; TUMOR CELLS, CULTURED; TUMOR MARKERS, BIOLOGICAL;

EID: 0032786494     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.286.5447.2176     Document Type: Article

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42. 2 in buffer, followed by washing in buffer and then water. Sections were then counterstained with hematoxylin, dehydrated in a graded series of ethanols and xylene, and coverslipped. Slides were reviewed by light microscopy. Positive reactions with DAB were identified as a dark brown reaction product Sections were photographed on a Nikon Optiphot microscope (Nikon Instruments, Melville, NY).
43. Characterization of soft tissue sarcomas in cis-Nf1:p53 mice. Histopathological examination was performed on all tumors obtained from animals at the termination of the experiment. Soft tissue tumors were classified in accordance with 1994 World Health Organization criteria. Tumor masses were removed under sterile conditions and measured. Small pieces of tumor tissue were removed for histological processing, DNA isolation, and establishment of tumor cell lines. Tumor samples were fixed in either Bouin's fixative (for hematoxylin and eosin staining) or 10% formalin (for immunohistochemistry) and processed for paraffin embedding and sectioning at 5 to 7 μm. Tumor sections were immunostained with S100 antibody (anti-S100) (Novocastra), antidesmin (Signet), anti-α-actin (Boehringer), or anti-myoglobin (Signet) and visualized by the Vectastain Elite ABC peroxidase method (Vector). Tumor DNA was genotyped by three-primer PCRs as described above.
44. Nf1/p53 tumor-derived cell lines were isolated as follows: Overlying skin and hair were removed from the tumor mass and then the tumor mass immersed briefly in Dulbecco's phosphate-buffered saline and in a solution of penicillin and streptomycin (Gibco). Small pieces of the tumor mass were minced in Dulbecco's modified Eagle's medium (DMEM) [supplemented with 10% heat-inactivated fetal calf serum (HIFCS), penicillin and streptomycin, and nonessential amino acids] (Gibco) with watchmaker's forceps and fine curved scissors. Tumor pieces were allowed to attach to 60-mm plastic tissue culture dishes, and clonal cell lines were established from tumor outgrowths after four to six passages.
45. 2 culture flasks in Nonidet P-40 lysis buffer containing protease inhibitors (Sigma). Insoluble (SMA, GFAP) and soluble (c-neu, S100) fractions were subjected to SDS-polyacrylamide gel electrophoresis on 8% to 10% minigels. After protein transfer, nitrocellulose membranes were blocked with 2% bovine serum albumin in tris-buffered saline and incubated with primary antibody overnight at 4°C Specific protein bands were visualized with Vectastain Elite ABC peroxidase kits (Vector Laboratories), or with Immun-Star kits (BioRad), according to the manufacturers' instructions.
46. Supported by NIH grant NS34296 and the National Neurofibromatosis Foundation (L.F.P.) and by a grant from the Cancer Association of Greater New Orleans (K.S.V.). We thank T. Jacks and colleagues for sharing unpublished results, S. Colvin and J. Richardson for early assistance with histopathology, and members of the Parada lab for helpful discussions.