Endogenous expression of Hras(G12V) induces developmental defects and neoplasms with copy number imbalances of the oncogene Journal Article

   


Authors: Chen, X.; Mitsutake, N.; LaPerle, K.; Akeno, N.; Zanzonico, P.; Longo, V. A.; Mitsutake, S.; Kimura, E. T.; Geiger, H.; Santos, E.; Wendel, H. G.; Franco, A.; Knauf, J. A.; Fagin, J. A.
Article Title: Endogenous expression of Hras(G12V) induces developmental defects and neoplasms with copy number imbalances of the oncogene
Abstract: We developed mice with germline endogenous expression of oncogenic Hras to study effects on development and mechanisms of tumor initiation. They had high perinatal mortality, abnormal cranial dimensions, defective dental ameloblasts, and nasal septal deviation, consistent with some of the features of human Costello syndrome. These mice developed papillomas and angiosarcomas, which were associated with Hras(G12V) allelic imbalance and augmented Hras signaling. Endogenous expression of Hras(G12V) was also associated with a higher mutation rate in vivo. Tumor initiation by Hras(G12V) likely requires augmentation of signal output, which in papillomas and angiosarcomas is achieved via increased Hras-gene copy number, which may be favored by a higher mutation frequency in cells expressing the oncoprotein.
Keywords: immunohistochemistry; signal transduction; controlled study; mutation; clinical feature; disease course; nonhuman; neoplasms; mouse; animals; mice; allele; animal tissue; mus; disease association; genetic predisposition to disease; gene expression; embryo; animal experiment; animal model; alleles; tomography, x-ray computed; in vivo study; angiosarcoma; mice, transgenic; oncogenes; gene expression regulation, developmental; gene number; oncogene; gene expression regulation, neoplastic; allele copy number; costello syndrome; papilloma; senescence; ameloblast; developmental disorder; mutation rate; skin papilloma; dna mutational analysis; ras proteins
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 106
Issue: 19
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2009-05-12
Start Page: 7979
End Page: 7984
Language: English
DOI: 10.1073/pnas.0900343106
PUBMED: 19416908
PROVIDER: scopus
PMCID: PMC2674938
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-66049085164&partnerID=40&md5=428e718e1c646f3a915eff2513b78877
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "CODEN: PNASA" - "Source: Scopus"
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. James A Fagin
    181 Fagin
  2. Jeffrey A Knauf
    61 Knauf
  3. Krista La Perle
    20 La Perle
  4. Pat B Zanzonico
    357 Zanzonico
  5. Aime Trzcienski Franco
    4 Franco
  6. Xu Chen
    6 Chen
  7. Hans Guido Wendel
    102 Wendel
  8. Valerie Ann Longo
    37 Longo
Related MSK Work