Increased tumor cell proliferation in murine tumors with decreasing dosage of wild-type p53

Stuart D. Tyner, Jene Choi, Rodolfo Laucirica, Richard J. Ford, Lawrence A. Donehower

Research output: Contribution to journalArticle

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Abstract

A number of transgenic animal model systems have addressed the mechanistic role of p53 loss in tumor progression. However, many of these tumor models have analyzed p53 function in the context of other transgenes expressing activated oncogenes or defective tumor suppressor genes generated by gene targeting. To examine the role of p53 loss independent of other exogenous oncogenic influences, we analyzed some of the biological aspects of tumor formation and progression in p53-knockout mice containing a null germline p53 allele. We analyzed tumors from p53-/-, p53+/-, and p53+/+ littermates. Some of the p53+/tumors had lost the remaining p53 allele (p53+/- loss of heterozygosity), whereas others retained the allele (p53+/- ). In this report, we show that loss or absence of p53 conferred a tumor growth advantage by increasing the rate of cellular proliferation in a p53 dosage-dependent manner. The apoptotic levels in tumor tissue were found to be modest and not significantly dependent on p53 status. These results contrast with those from some other p53-deficient tumor models, in which p53 loss was associated with more rapid tumor progression through abrogated apoptosis. Finally, as p53 has been shown to regulate certain angiogenic factors, we examined the levels of angiogenesis in p53-containing and p53- deficient tumors. We found no p53-dependent differences in the levels of tumor angiogenesis measured by intratumoral microvessel density.

Original languageEnglish (US)
Pages (from-to)197-208
Number of pages12
JournalMolecular Carcinogenesis
Volume24
Issue number3
DOIs
StatePublished - Apr 20 1999
Externally publishedYes

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Cell Proliferation
Neoplasms
Alleles
Genetically Modified Animals
Gene Targeting
Angiogenesis Inducing Agents
Loss of Heterozygosity
Microvessels
Tumor Suppressor Genes
Transgenes
Oncogenes
Knockout Mice
Animal Models
Apoptosis
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Cite this

Increased tumor cell proliferation in murine tumors with decreasing dosage of wild-type p53. / Tyner, Stuart D.; Choi, Jene; Laucirica, Rodolfo; Ford, Richard J.; Donehower, Lawrence A.

In: Molecular Carcinogenesis, Vol. 24, No. 3, 20.04.1999, p. 197-208.

Research output: Contribution to journalArticle

Tyner, Stuart D. ; Choi, Jene ; Laucirica, Rodolfo ; Ford, Richard J. ; Donehower, Lawrence A. / Increased tumor cell proliferation in murine tumors with decreasing dosage of wild-type p53. In: Molecular Carcinogenesis. 1999 ; Vol. 24, No. 3. pp. 197-208.
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