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Silencing of Wnt-1 by siRNA Induces Apoptosis of MCF-7 Human Breast Cancer Cells

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, Monika Lamparska-Przybysz

Cancer Biol Ther. 2008 Feb;7(2):268-74.

PMID: 18059186

Abstract:

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 Ca(2+)-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.
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 48 h (p < 0.01).
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.
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 anti-cancer drug.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248785	WNT-1 human			Price

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