Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Point mutations of the transmembrane domain coding region of the neu proto-oncogene in N-nitroso-N-ethylurea-induced hamster neurofibromas were found at high frequency (93%; 14 of 15). They involved codons 659 as well as 658, the latter not having been reported previously in rat tumors. The mutational change was seen even in the early stage neurofibroma. On the other hand, no mutations were detected in melanomas or Wilms' tumors induced in the same N-nitroso-N-ethylurea-treated animals, even when the melanomas demonstrated extensive schwannian differentiation. Moreover, any human Schwann cell tumors including neurofibroma, schwannoma, and malignant schwannoma did not show the mutation of c-erbB-2 gene (0 of 34), which is homologous to the hamster neu. Since high expression of neu mRNA is evident in the hamster Schwann cell at the late gestational and neonatal stages, transplacental administration of N-nitroso-N-ethylurea is considered to interact directly to carcinogenesis of the hamster Schwann cell through neu gene mutation.
 ...
PMID:neu proto-oncogene mutation is specific for the neurofibromas in a N-nitroso-N-ethylurea-induced hamster neurofibromatosis model but not for hamster melanomas and human Schwann cell tumors. 790 99

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.
 ...
PMID:Wild type neu transgene counteracts mutant homologue in malignant transformation of rat Schwann cells. 864 33

Inbred rodent strains with differing sensitivity to experimental tumor induction provide model systems for the detection of genes that either are responsible for cancer predisposition or modify the process of carcinogenesis. Rats of the inbred BD strains differ in their susceptibility to the induction of neural tumors by N-ethyl-N-nitrosourea (EtNU). Newborn BDIX rats that are exposed to EtNU (80 microg/g body weight; injected s.c.) develop malignant schwannomas predominantly of the trigeminal nerves with an incidence >85%, whereas BDIV rats are entirely resistant. A T:A-->A:T transversion mutation at nucleotide 2012 of the neu (erbB-2) gene on chromosome 10, presumably the initial event in EtNU-induced schwannoma development, is later followed by loss of the wild-type neu allele. Genetic crosses between BDIX and BDIV rats served: (a) to investigate the inheritance of susceptibility; (b) to obtain animals informative for the mapping of losses of heterozygosity (LOH) in tumors with polymorphic simple sequence length polymorphisms (SSLPs); and (c) to localize genes associated with schwannoma susceptibility by linkage analysis with SSLPs. Schwannoma development was strongly suppressed in F1 animals (20% incidence). All of the F1 schwannomas displayed LOH on chromosome 10, with a consensus region on the telomeric tip encompassing D10Rat3, D10Mgh16 and D10Rat2 but excluding neu. A strong bias toward losing the BDIV alleles suggests the involvement of a BDIV-specific tumor suppressor gene(s). Targeted linkage analysis with chromosome 10 SSLPs in F2 intercross and backcross animals localized schwannoma susceptibility to a region around D10Wox23, 30 cM centromeric to the tip. Ninety-four % of F1 tumors exhibited additional LOH at this region. Two distinct loci on chromosome 10 may thus be connected with susceptibility to the induction and development of schwannomas in rats exposed to EtNU.
 ...
PMID:Ethylnitrosourea-induced development of malignant schwannomas in the rat: two distinct loci on chromosome of 10 involved in tumor susceptibility and oncogenesis. 1007 Sep 70