Down-regulation of SFRP1 in a mammary epithelial cell line promotes the development of a CD44high/CD24low population which is invasive and resistant to anoikis Public Deposited
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Hugh, Jeremy M
- Other Affiliation: Biology Department, University of Massachusetts, Amherst, MA 01003, USA
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, School of Medicine
- Other Affiliation: Pioneer Valley Life Sciences Institute, Baystate Medical Center, Springfield, MA 01199, USA; Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA
Gauger, Kelly J
- Other Affiliation: Pioneer Valley Life Sciences Institute, Baystate Medical Center, Springfield, MA 01199, USA; Biology Department, University of Massachusetts, Amherst, MA 01003, USA
- Abstract Background 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. 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. Results When 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. Conclusion Our study suggests that loss of SFRP1 allows non-malignant cells to acquire characteristics associated with breast cancer cells.
- Date of publication
- May 7, 2009
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- In Copyright
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- Kelly J Gauger et al.; licensee BioMed Central Ltd.
- Journal title
- Cancer Cell International
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- Journal issue
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- Is the article or chapter peer-reviewed?
- Bibliographic citation
- Cancer Cell International. 2009 May 07;9(1):11
- Open Access
- BioMed Central Ltd
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|Primers used for real-time PCR analysis. A list of the forward and reverse primers utilized in the real-time PCR assays described in the manuscript.||2019-05-06||Public||