Abstract
BackgroundThe Wnt family of secreted proteins is implicated in the regulation of cell fate during development, as well as in cell proliferation, morphology, and migration. Aberrant activation of the Wnt/β-catenin signaling pathway leads to the development of several human cancers, including breast cancer. Secreted frizzled-related protein 1 (SFRP1) antagonizes this pathway by competing with the Frizzled receptor for Wnt ligands resulting in an attenuation of the signal transduction cascade. Loss of SFRP1 expression is observed in breast cancer, along with several other cancers, and is associated with poor patient prognosis. However, it is not clear whether the loss of SFRP1 expression predisposes the mammary gland to tumorigenesis.ResultsWhen SFRP1 is knocked down in a non-malignant immortalized mammary epithelial cell line (76 N TERT), nuclear levels of β-catenin rise and the Wnt pathway is stimulated. The SFRP1 knockdown cells exhibit increased expression of the pro-proliferative Cyclin D1 gene and increased cellular proliferation, undergo a partial epithelial-mesenchymal transition (EMT), are resistant to anchorage-independent cell death, exhibit increased migration, are significantly more invasive, and exhibit a CD24low/CD44high cell surface marker expression pattern.ConclusionOur study suggests that loss of SFRP1 allows non-malignant cells to acquire characteristics associated with breast cancer cells.
Highlights
The Wnt family of secreted proteins is implicated in the regulation of cell fate during development, as well as in cell proliferation, morphology, and migration
Characterization of 76 N TERT cells stably transfected with siSFRP1 To evaluate the effects of Secreted frizzled-related protein 1 (SFRP1) down-regulation in an immortal mammary epithelial cell line, 76 N TERT cells were stably transfected with the pSUPER-siSFRP1 construct
Real-time PCR analysis revealed that the mRNA expression levels of SFRP1 are significantly lower in TERTsiSFRP1 cells when compared with TERT-pSUPER cells (Figure 1A)
Summary
The Wnt family of secreted proteins is implicated in the regulation of cell fate during development, as well as in cell proliferation, morphology, and migration. Aberrant activation of the Wnt/β-catenin signaling pathway leads to the development of several human cancers, including breast cancer. Members of the Wnt family of secreted proteins regulate cellular proliferation, morphology, and migration by way of β-catenin-mediated transcriptional activation [2,3,4]. Cancer Cell International 2009, 9:11 http://www.cancerci.com/content/9/1/11 genes, contributes to the genesis of a wide range of human cancers [2]. Such mutations are rarely observed in breast cancer despite the finding that β-catenin is stabilized in a majority of human breast tumors [5]. Aberrantly activated Wnt signaling leads to inappropriate mammary gland development and mammary tumorigenesis in mice [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
