Related Experiment Video
Updated: Jul 7, 2026
The Soft Agar Colony Formation Assay
Published on: October 27, 2014
Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer
H Suzuki1, M Toyota, H Carraway
1First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan.
Abstract:
Although mutation of APC or CTNNB1 (beta-catenin) is rare in breast cancer, activation of Wnt signalling is nonetheless thought to play an important role in breast tumorigenesis, and epigenetic silencing of Wnt antagonist genes, including the secreted frizzled-related protein (SFRP) and Dickkopf (DKK) families, has been observed in various tumours. In breast cancer, frequent methylation and silencing of SFRP1 was recently documented; however, altered expression of other Wnt antagonist genes is largely unknown. In the present study, we found frequent methylation of SFRP family genes in breast cancer cell lines (SFRP1, 7 out of 11, 64%; SFRP2, 11 out of 11, 100%; SFRP5, 10 out of 11, 91%) and primary breast tumours (SFRP1, 31 out of 78, 40%; SFRP2, 60 out of 78, 77%; SFRP5, 55 out of 78, 71%). We also observed methylation of DKK1, although less frequently, in cell lines (3 out of 11, 27%) and primary tumours (15 out of 78, 19%). Breast cancer cell lines express various Wnt ligands, and overexpression of SFRPs inhibited cancer cell growth. In addition, overexpression of a beta-catenin mutant and depletion of SFRP1 using small interfering RNA synergistically upregulated transcriptional activity of T-cell factor/lymphocyte enhancer factor. Our results confirm the frequent methylation and silencing of Wnt antagonist genes in breast cancer, and suggest that their loss of function contributes to activation of Wnt signalling in breast carcinogenesis.
Insights
Epigenetic silencing of Wnt antagonist genes, like secreted frizzled-related proteins (SFRPs), is common in breast cancer. This loss of function contributes to Wnt signaling activation, promoting breast cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Wnt signaling is implicated in breast tumorigenesis.
- While APC/CTNNB1 mutations are rare, epigenetic silencing of Wnt antagonists like SFRP and DKK families is observed in tumors.
- Previous studies documented SFRP1 silencing, but other Wnt antagonists in breast cancer remain understudied.
Purpose of the Study:
- To investigate the methylation status and expression of Wnt antagonist genes in breast cancer.
- To determine the role of Wnt antagonist gene silencing in breast cancer development.
Main Methods:
- Analyzed methylation frequency of SFRP family genes (SFRP1, SFRP2, SFRP5) and DKK1 in breast cancer cell lines and primary tumors.
- Assessed the impact of SFRP overexpression on cancer cell growth.
- Investigated the effect of beta-catenin mutant overexpression and SFRP1 depletion on T-cell factor/lymphocyte enhancer factor activity.
Main Results:
- Frequent methylation and silencing of SFRP family genes were observed in breast cancer cell lines and primary tumors (SFRP1: 64% & 40%, SFRP2: 100% & 77%, SFRP5: 91% & 71%).
- DKK1 methylation was also found, though less frequently (27% in cell lines, 19% in tumors).
- Overexpression of SFRPs inhibited breast cancer cell growth, and SFRP1 depletion alongside beta-catenin mutant overexpression enhanced Wnt signaling.
Conclusions:
- Breast cancer frequently exhibits epigenetic silencing of Wnt antagonist genes.
- Loss of Wnt antagonist function contributes to Wnt signaling activation in breast carcinogenesis.
- These findings highlight Wnt antagonists as potential therapeutic targets in breast cancer.
Related Concept Videos
01:37Epigenetic Regulation
X-chromosome...
01:46Epigenetic Regulation
02:54Canonical Wnt Signaling Pathway
02:54Canonical Wnt Signaling Pathway
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...