'Designer' tumors in mice

Oncogene. 2004 Feb 26;23(8):1558-65. doi: 10.1038/sj.onc.1207275.

Abstract

We have developed and tested successfully a general method based on Cre-mediated recombination that can be used for ubiquitous or tissue-specific expression of protein products, including tumor-inducing oncoproteins. Depending on the specificity of a chosen promoter driving cre expression, tumors develop by design in bitransgenic mouse progeny derived by crossing Cre-producing mice with partners carrying a dormant oncogenic transgene (targeted into the 3' noncoding region of the cytoplasmic beta-actin locus) that becomes functional after excision of a 'floxed' DNA segment. To provide proof-of-principle, we have used as models transgenes encoding the polyomavirus middle T antigen (PVMT) and the T antigens of the SV40 early region (SVER). Cre-dependent activation of widespread SVER expression resulted in hyperplasias or invasive tumors affecting particular visceral smooth muscles, whereas Cre-dependent, mammary gland-specific expression of PVMT-induced adenocarcinomas, according to plan. Unexpectedly, we also encountered spontaneous (Cre-independent) oncogene expression occurring as a rare event, which simulates the initiation of sporadic tumors and leads to PVMT-induced hemangiomas and mammary carcinomas or SVER-induced disseminated sarcomas, thus, revealing particular tissue susceptibilities to the actions of these oncoproteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / genetics
  • Animals
  • Antigens, Polyomavirus Transforming / genetics
  • Disease Models, Animal*
  • Mice
  • Mice, Transgenic
  • Muscle, Smooth / pathology
  • Mutagenesis, Insertional / methods*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Oncogenes
  • Promoter Regions, Genetic
  • Transgenes

Substances

  • Actins
  • Antigens, Polyomavirus Transforming
  • Oncogene Proteins