Centrosome abnormalities, recurring deletions of chromosome 4, and genomic amplification of HER2/neu define mouse mammary gland adenocarcinomas induced by mutant HER2/neu

Cristina Montagna, Eran R. Andrechek, Hesed Padilla-Nash, William J. Muller, Thomas Ried

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

The conditional expression of activated HER2/neu gene under its endogenous promoter in the mammary epithelium of the mouse results in accelerated lobular development and focal mammary tumors. Carcinogenesis, however, requires amplification and considerably increased expression levels of oncogenic neu. Deducing from the multiple genetic aberrations required for human breast cancer to develop, we hypothesized that in addition to the over-expression of an activated HER2/neu, secondary aberrations would occur. We have therefore conducted a genomic screen for chromosomal imbalances and translocations using comparative genomic hybridization and spectral karyotyping. The results reveal a moderate degree of chromosomal instability and micronuclei formation in short-term cultures established from primary tumors. Genomic instability appears to be linked to the amplification of functional centrosomes, a phenomenon that we frequently observed in other tumor types. Seventy per cent of the tumors revealed genomic amplification of HER2/neu, often in the form of double minute chromosomes, which correlated with recurring loss of mouse chromosome 4D-E, a region that is orthologous to distal human chromosome 1p. It is likely that this region contains putative tumor suppressor genes whose inactivation is required for tumor formation in this model of human breast cancer.

Original languageEnglish (US)
Pages (from-to)890-898
Number of pages9
JournalOncogene
Volume21
Issue number6
DOIs
Publication statusPublished - Jan 31 2002
Externally publishedYes

    Fingerprint

Keywords

  • Breast cancer model
  • Centrosome
  • Double minutes (DMs)
  • Genomic instability
  • HER2/neu
  • Spectral karyotyping (SKY)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this