p53-dependent apoptosis suppresses tumor growth and progression in vivo

Cell. 1994 Aug 26;78(4):703-11. doi: 10.1016/0092-8674(94)90534-7.


To determine the contribution of p53 loss to tumor progression, we have induced abnormal proliferation in the brain choroid plexus epithelium of transgenic mice using a SV40 T antigen fragment that perturbs pRB family function but does not affect p53 function. Tumors induced by this mutant develop slowly compared with those induced by wild-type T antigen. Suppressed tumor growth is directly attributable to p53 function, since rapid tumor development occurs when the T antigen fragment is expressed in p53-null mice. In p53-heterozygous mice, stochastic loss of the wild-type p53 allele results in the focal emergence of aggressive tumor nodules characteristic of tumor progression. In each case, aggressive tumor development in the absence of p53 function corresponds to a decrease in the level of apoptosis. These results provide in vivo evidence that p53-dependent apoptosis, occurring in response to oncogenic events, is a critical regulator of tumorigenesis.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / genetics
  • Apoptosis / physiology*
  • Base Sequence
  • Cell Transformation, Neoplastic*
  • Choroid Plexus / physiology
  • Choroid Plexus Neoplasms / genetics
  • Choroid Plexus Neoplasms / pathology*
  • Crosses, Genetic
  • Epithelium
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Molecular Sequence Data
  • Mutation / physiology
  • Tumor Suppressor Protein p53 / physiology*


  • Antigens, Polyomavirus Transforming
  • Tumor Suppressor Protein p53