Landes Bioscience Journals: Cancer Biology & Therapy

Editor-in-Chief
Wafik S. El-Deiry, M.D., Ph.D.
University of Pennsylvania
Philadelphia, PA

Print ISSN: 1538-4047
Online ISSN: 1555-8576

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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

Volume 7, Issue 2

February 2008
Pages: 268 - 274

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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.