Endogenous expression of HrasG12V induces developmental defects and neoplasms with copy number imbalances of the oncogene Academic Article uri icon

Overview

MeSH Major

  • Neoplasms
  • ras Proteins

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.

publication date

  • May 12, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2674938

Digital Object Identifier (DOI)

  • 10.1073/pnas.0900343106

PubMed ID

  • 19416908

Additional Document Info

start page

  • 7979

end page

  • 84

volume

  • 106

number

  • 19