Fhit expression protects against HER2-driven breast tumor development: Unraveling the molecular interconnections

Francesca Bianchi, Elda Tagliabue, Sylvie Ménard, Manuela Campiglio

Research output: Contribution to journalArticle

Abstract

The tumor suppressor gene FHIT is inactivated by genetic and epigenetic changes, i.e., loss of heterozygosity or promoter hypermethylation, in common human cancers. We recently showed that Fhit protein levels can be regulated by Fhit proteasome degradation mediated by EGF-dependent activation of EGFR family members, including HER2, whose overexpression is linked to poor prognosis in breast cancer. Analysis of a series of 384 human primary breast carcinomas revealed low/absent Fhit protein levels more frequently in HER2-overexpressing tumors. To test for a possible complementation of the FHIT and HER2 genes, tumor incidence was assessed in mice carrying one inactivated Fhit allele (Fhit+/-) crossed with FVB/N mice carrying the rat HER2/neu proto-oncogene driven by the mouse mammary tumor virus promoter. All Fhit heterozygous mice developed mammary tumors, whereas when both Fhit alleles (Fhit+/+) were present, tumor incidence was reduced in 27% of the mice, which remained tumor-free at twenty months. These findings suggest a protective role for FHIT in HER2-driven mammary tumors. Together, these data argue for the cooperation between Fhit and HER2 in breast carcinogenesis.

Original languageEnglish
Pages (from-to)643-646
Number of pages4
JournalCell Cycle
Volume6
Issue number6
Publication statusPublished - Mar 15 2007

Keywords

  • Breast tumors
  • EGFR
  • Fhit
  • HER2
  • Signaling

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

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