Increased tumor proliferation and genomic instability without decreased apoptosis in MMTV-ras mice deficient in p53

Jeff E. Hundley, Steven K. Koester, Dean A. Troyer, Susan G. Hilsenbeck, Mark A. Subler, Jolene J. Windle

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

We have used an in vivo tumor model to evaluate the consequences of p53 tumor suppressor protein deficiency in a tissue-specific context. By breeding MMTV-ras transgenic mice, which are highly susceptible to the development of mammary and salivary tumors, with p53(-/-) mice, we generated three classes of animals which contained the MMTV-ras transgene but differed in their p53 functional status (ras/p53(+/+), ras/p53(+/-), or ras/p53(-/-)). ras/p53(-/- ) mice developed tumors more rapidly than animals of the other two genotypes; however, the distribution of tumors was unexpectedly altered. Whereas the most frequently observed tumors in ras/p53(+/+) and ras/p53(+/-) mice were of mammary origin, ras/p53(-/-) mice developed primarily salivary tumors. In addition, the mammary and salivary tumors from ras/p53(-/-) mice consistently exhibited a number of unfavorable characteristics, including higher histologic grades, increased growth rates, and extensive genomic instability and heterogeneity, relative to tumors from ras/p53(+/+) mice. Interestingly, the increased growth rates of ras/p53(-/-) tumors appear to be due to impaired cell cycle regulation rather than decreased apoptosis, suggesting that p53-mediated tumor suppression can occur independent of its role in apoptosis.

Original languageEnglish (US)
Pages (from-to)723-731
Number of pages9
JournalMolecular and cellular biology
Volume17
Issue number2
DOIs
StatePublished - Feb 1997
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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