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

beta-Transducin repeat-containing proteins (beta-TrCP) serve as substrate recognition component of E3 ubiquitin ligases that control stability of important regulators of cell cycle and signal transduction. beta-TrCP function is essential for the induction of nuclear factor kappaB transcriptional act...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2005-03, Vol.65 (5), p.1904-1908
Main Authors: TANG, Weigang, YING LI, DUONAN YU, THOMAS-TIKHONENKO, Andrei, SPIEGELMAN, Vladimir S, FUCHS, Serge Y
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Apoptosis - drug effects
beta-Transducin Repeat-Containing Proteins - antagonists & inhibitors
beta-Transducin Repeat-Containing Proteins - genetics
beta-Transducin Repeat-Containing Proteins - metabolism
Biological and medical sciences
Breast Neoplasms - genetics
Colony-Forming Units Assay
Doxorubicin - therapeutic use
Drug Synergism
Female
Gene Expression Regulation, Neoplastic
Genes, Dominant
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Mutation - genetics
Paclitaxel - therapeutic use
Pharmacology. Drug treatments
RNA, Small Interfering - pharmacology
Tamoxifen - therapeutic use
Tumor Cells, Cultured
Tumors
Ubiquitin-Protein Ligases - antagonists & inhibitors
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
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Summary:beta-Transducin repeat-containing proteins (beta-TrCP) serve as substrate recognition component of E3 ubiquitin ligases that control stability of important regulators of cell cycle and signal transduction. beta-TrCP function is essential for the induction of nuclear factor kappaB 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 beta-TrCP either by RNAi approach or by forced expression of a dominant-negative beta-TrCP mutant suppresses growth and survival of human breast cancer cells. In addition, inhibition of beta-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 beta-TrCP might be beneficial for anticancer therapies.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-04-2597