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Research Paper

Silencing of Wnt-1 by siRNA induces apoptosis of MCF-7 human breast cancer cells

Maciej Wieczorek, Aleksandra Paczkowska, Piotr Guzenda, Maria Majorek, Andrzej K. Bednarek and Monika Lamparska-Przybysz

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Objective: Wnt family of secreted-type glycoproteins plays key role in carcinogenesis and embryogenesis. Signals of Wnts are transduced through seven-transmembrane-type Wnt receptors encoded by Frizzled (Fzd) genes to the beta-catenin - Tcf pathway, the c-Jun-N-terminal kinase (JNK) pathway or the Ca2+-releasing pathway. Aberrant activation of the Wnt/beta-catenin signaling pathway is associated with a variety of human cancers. In human breast cancer, evidence of beta-catenin accumulation implies that the canonical Wnt signaling pathway is active in over 50% of carcinomas. Methods: To examine if Wnt-1 signal is essential for cancer cell survival, we investigated the effect of Wnt-1 gene silencing in triggering of apoptosis in MCF-7 breast cancer cell line. Light microscopy, viability/cytotoxicity tests, flow cytometry, real-time PCR and western blotting were used for evaluation of the morphological features of cell death, percentage of apoptotic cells, Wnt-1 mRNA and protein level. Results: We found that in breast cancer cells overexpressing Wnt-1 siRNA anti-Wnt-1 induced apoptosis and caused changes in downstream proteins levels. Among treated cells there were 71% apoptotic cells in comparison to cells treated with scrambled siRNA (6%) and control cells (6%) after 48h (p<0.01). Conclusion: Our results significantly indicate that anti-Wnt-1 siRNA inhibits Wnt-1 signaling, inducing apoptosis in human breast cancer MCF-7 cells and thus may serve as a potential anticancer drug.

Authors

Maciej Wieczorek

Department of Research and Development, Celon Pharma Ltd., Lomianki, Poland

Aleksandra Paczkowska

Department of Research and Development, Celon Pharma Ltd., Lomianki, Poland

Piotr Guzenda

Department of Research and Development, Celon Pharma Ltd., Lomianki, Poland

Maria Majorek

Department of Research and Development, Celon Pharma Ltd., Lomianki, Poland

Andrzej K. Bednarek

Department of Molecular Cancerogenesis, Medical University of Lodz, Lodz, Poland.

Monika Lamparska-Przybysz

Department of Research and Development, Celon Pharma Ltd., Lomianki, Poland

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If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.