Targeting β-transducin repeat-containing protein E3 ubiquitin ligase augments the effects of antitumor drugs on breast cancer cells

Weigang Tang, Ying Li, Duonan Yu, Andrei Thomas-Tikhonenko, Vladimir S. Spiegelman, Serge Y. Fuchs

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

β-Transducin repeat-containing proteins (β-TrCP) serve as substrate recognition component of E3 ubiquitin ligases that control stability of important regulators of cell cycle and signal transduction. β-TrCP function is essential for the induction of nuclear factor κB transcriptional activities, which play a key role in proliferation and survival of cancer cells and are often constitutively up-regulated in human breast cancers. Here we show that inhibition of β-TrCP either by RNAi approach or by forced expression of a dominant-negative β-TrCP mutant suppresses growth and survival of human breast cancer cells. In addition, inhibition of β-TrCP augments the antiproliferative effects of anticancer drugs such as doxorubicin, tamoxifen, and paclitaxel on human mammary tumor cells. These data provide the proof of principle that targeting β-TrCP might be beneficial for anticancer therapies.

Original languageEnglish (US)
Pages (from-to)1904-1908
Number of pages5
JournalCancer Research
Volume65
Issue number5
DOIs
StatePublished - Mar 1 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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