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Circumventing drug resistance in breast cancer cells by down-regulating the Wnt/β-catenin pathway.

Multidrug resistance (MDR) is a major impediment to the treatment of breast cancer. Disseminated cancers are often inherently resistant to a broad spectrum of anti-cancer drugs or, after an initial response phase, become resistant to further treatment. The multidrug resistance 1 gene (MDR1) encodes the plasma membrane efflux pump, P-glycoprotein (P-gp), and is a direct target of the Wnt/β-catenin signaling pathway. Overexpression of P-gp increases active efflux of cytotoxic drugs from cells, lowering intracellular concentrations and promoting chemoresistance. Dr. Gengyin Zhou and colleagues at the Shandong University School of Medicine in P. R. China (Zhang, et al Cancer Lett. 2012 Apr 4. [Epub ahead of print]) established that the Frizzled 1 (FZD1) protein, an essential component of the Wnt/β-catenin pathway, is overexpressed in the multidrug resistant breast cancer cell sub-line MCF-7/ADM, in concert with P-gp. FZD1 silencing by plasmid-mediated expression of small interference RNA (siRNA) diminished P-gp levels, restoring sensitivity to four tested chemotherapy drugs, while also significantly decreasing cytoplasmic and nuclear β-catenin levels. FZD1 offers promise as a potential new target for reversing multidrug resistance in breast cancer.

Enzo Life Sciences offers comprehensive tools contributing to the understanding of the canonical Wnt/β –catenin pathway, as well as the analysis of multi-drug resistance transporters.

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