Acceleration of mouse mammary tumor virus-induced murine mammary tumorigenesis by a p53172H transgene: Influence of FVB background on tumor latency and identification of novel sites of proviral insertion

Gouri Chatterjee, Andrea Rosner, Yi Han, Edward T. Zelazny, Baolin Li, Robert Cardiff, Archibald S. Perkins

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Abstract

We previously showed that a mammary-specific dominant-negative p53 transgene (WAP-p53172H) could accelerate ErbB2-induced mammary tumorigenesis in mice, but was not tumorigenic on its own. To identify other genes that cooperate with WAP-p53172H in tumorigenesis, we performed mouse mammary tumor virus (MMTV) proviral mutagenesis. We derived F1, N2, and N4/N5 mice from p53172H transgenic FVB mice backcrossed onto MMTV+ C3H/He mice. Results show the latency of MMTV tumorigenesis is correlated with FVB contribution. F1 tumors had the shortest latency (217 days), had a higher rate of metastasis, and were less differentiated than the N2 and N4/N5 tumors. The latency was 269 days in N2 mice, and lengthened to 346 days in N4/N5 mice. p53172H significantly accelerated MMTV tumorigenesis only in N2 mice, indicating cooperativity between p53172H and MMTV in this cohort. To identify genes that may be causally involved in MMTV-induced mammary tumorigenesis, we identified 60 sites of proviral insertion in the N2 tumors. Among the insertions in p53172H transgenic tumors were 10 genes not previously found as sites of MMTV insertion including genes involved in signaling (Pdgfra, Pde1b, Cnk1), cell adhesion (Cd44), angiogenesis (Galgt1), and transcriptional regulation (Olig1, Olig2, and Uncx4.1). These may represent cellular functions that are likely not deregulated by mutation in p53.

Original languageEnglish (US)
Pages (from-to)2241-2253
Number of pages13
JournalAmerican Journal of Pathology
Volume161
Issue number6
DOIs
StatePublished - Dec 1 2002

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Mouse mammary tumor virus
Transgenes
Carcinogenesis
Breast
Neoplasms
Genes
Inbred C3H Mouse
Insertional Mutagenesis
Cell Adhesion
Mutagenesis
Transgenic Mice
Neoplasm Metastasis
Mutation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Acceleration of mouse mammary tumor virus-induced murine mammary tumorigenesis by a p53172H transgene : Influence of FVB background on tumor latency and identification of novel sites of proviral insertion. / Chatterjee, Gouri; Rosner, Andrea; Han, Yi; Zelazny, Edward T.; Li, Baolin; Cardiff, Robert; Perkins, Archibald S.

In: American Journal of Pathology, Vol. 161, No. 6, 01.12.2002, p. 2241-2253.

Research output: Contribution to journalArticle

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