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Requirement of Pygopus 2 in breast cancer
Phillip G P Andrews1, Blue B Lake, Catherine Popadiuk
1Terry Fox Cancer Research Laboratories, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, A1B 3V6, Canada.
Abstract:
The development of novel therapeutic strategies for breast cancer requires the identification of molecular targets involved in malignancy. Human Pygopus (Pygo)-1 and -2 are recently discovered components of the Wnt signaling pathway required for beta-Catenin/Tcf dependent transcription in embryos and colorectal cancer cells, but the role of these proteins in malignant cell growth and survival has not yet been determined. We report the expression and requirement for proliferation of hPygo2 in breast cancer cells. hPygo2 protein was overexpressed in malignant breast tumors and in the nuclei of five breast cancer cell lines, but was not expressed in the nuclei of non-malignant breast cells. Phosphorothioated antisense oligonucleotides were used to specifically knockdown expression hPygo2 in Mcf-7 and MDA-MB-468 cell lines. hPygo2 was required for the growth, in tissue culture and anchorage-independent assays, of both cell lines and for the expression of the Wnt target gene Cyclin D1. We conclude that hPygo2 is highly expressed in, and required for the growth of breast carcinoma cells.
Insights
Human Pygopus (Pygo)-2 is overexpressed in breast cancer cells and tumors. This protein is essential for the proliferation and survival of breast carcinoma cells, making it a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Novel therapeutic strategies for breast cancer necessitate identifying molecular targets driving malignancy.
- Human Pygopus (Pygo)-1 and -2 are Wnt signaling pathway components crucial for beta-Catenin/Tcf dependent transcription.
- The specific role of Pygo proteins in breast cancer cell growth and survival remains largely undetermined.
Purpose of the Study:
- To investigate the expression and functional requirement of human Pygopus (hPygo)-2 in breast cancer cells.
- To determine if hPygo2 plays a role in the proliferation and survival of malignant breast cells.
Main Methods:
- Quantitative analysis of hPygo2 protein expression in breast tumors and cell lines.
- Utilized phosphorothioated antisense oligonucleotides for specific hPygo2 knockdown in MCF-7 and MDA-MB-468 cell lines.
- Assessed cell proliferation via tissue culture and anchorage-independent assays, and measured Wnt target gene expression (Cyclin D1).
Main Results:
- hPygo2 protein was significantly overexpressed in malignant breast tumors and breast cancer cell lines, specifically localized to the nucleus.
- hPygo2 expression was absent in the nuclei of non-malignant breast cells.
- Knockdown of hPygo2 inhibited proliferation in both tested breast cancer cell lines and reduced Cyclin D1 expression.
Conclusions:
- hPygo2 is highly expressed in breast carcinoma cells and is required for their growth and proliferation.
- hPygo2 represents a potential molecular target for developing new breast cancer therapies.
