An in vivo study of Cdh1/APC in breast cancer formation

Takeo Fujita, Weijun Liu, Hiroyoshi Doihara, Yong Wan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in several types of tumorigenesis. Our previous studies have shown the potential role of Cdh1/APC in regulating tumor formation via governing the Skp2-p27-cyclinE/CDK2 axis. In this work, we used a xenograft mouse breast cancer model to identify the mechanism by which Cdh1/APC potentially suppresses tumor growth in vivo. Here, we report that depletion of Cdh1 results in a significant enhancement of the breast tumor proliferation, while elevated Cdh1 leads to suppression of breast tumor growth. Analysis of breast tissue arrays has indicated that higher levels of Cdh1 are associated with normal breast epithelial tissues whereas lower Skp2 expression and elevated p27 levels are detected. Conversely, the percentage of breast cancer tissues stained positive for Cdh1 and p27 are significantly lower with higher Skp2 levels. Thus, the E3 ligase, Cdh1/APC, may inhibit breast tumor growth via regulating Skp2-p27 mediated cell cycle progression.

Original languageEnglish
Pages (from-to)826-836
Number of pages11
JournalInternational Journal of Cancer
Volume125
Issue number4
DOIs
Publication statusPublished - Aug 15 2009

Fingerprint

Breast Neoplasms
Breast
Growth
Tissue Array Analysis
Ubiquitin-Protein Ligases
Proteasome Endopeptidase Complex
Ubiquitin
Heterografts
Neoplasms
Cell Cycle
Carcinogenesis
Epithelium

Keywords

  • APC
  • Breast cancer
  • Cdh1
  • p27
  • Skp2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

An in vivo study of Cdh1/APC in breast cancer formation. / Fujita, Takeo; Liu, Weijun; Doihara, Hiroyoshi; Wan, Yong.

In: International Journal of Cancer, Vol. 125, No. 4, 15.08.2009, p. 826-836.

Research output: Contribution to journalArticle

Fujita, Takeo ; Liu, Weijun ; Doihara, Hiroyoshi ; Wan, Yong. / An in vivo study of Cdh1/APC in breast cancer formation. In: International Journal of Cancer. 2009 ; Vol. 125, No. 4. pp. 826-836.
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