Wild type neu transgene counteracts mutant homologue in malignant transformation of rat Schwann cells.
Mutational activation of the neu (erbB-2) receptor protein tyrosine kinase gene appears to be the triggering event in the process of oncogenesis induced by N-ethyl-N-nitrosourea (EtNU) in immature Schwann cells of the rat peripheral nervous system. Subsequent loss of the wild-type neu allele may represent a critical secondary step towards malignancy. Developmentally-regulated expression of a wild-type rat neu transgene (neu cDNA under the control of the rat Po promoter) in the Schwann cells of transgenic BDIX and Sprague-Dawley rats exposed to EtNU on postnatal day 1 results in a lower incidence of early atypical proliferates in the trigeminal nerve. Furthermore, re-introduction of the wild-type neu gene into homozygous neu mutant schwannoma cells counteracts the expression of the tumorigenic phenotype. The suppressive action of the wild-type gene over its mutationally activated oncogenic homologue underlines the critical function of the neu gene in the control of differentiation in the Schwann cell lineage, and provides evidence for the responsiveness of cellular phenotypes towards quantitative shifts in the dosage of wild-type vs mutant signal transducing molecules.
Nikitin
A Y
AY
Institute of Cell Biology (Cancer Research), University of Essen Medical School, Germany.
Jin
J J
JJ
Papewalis
J
J
Prokopenko
S N
SN
Pozharisski
K M
KM
Winterhager
E
E
Flesken-Nikitin
A
A
Rajewsky
M F
MF
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005038:Ethylnitrosourea; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018734:Genes, erbB-2; D006720:Homozygote; D008969:Molecular Sequence Data; D009154:Mutation; D009442:Neurilemmoma / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000473:pathology / Q000502:physiology*; D014162:Transfection; D019076:Transgenes; D014276:Trigeminal Nerve / Q000166:cytology
D005038:Ethylnitrosourea