Targeting β-Transducin Repeat–Containing Protein E3 Ubiquitin Ligase Augments the Effects of Antitumor Drugs on Breast Cancer Cells

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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.