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WISP-1 is a Wnt-1- and beta-catenin-responsive oncogene
L Xu1, R B Corcoran, J W Welsh
1Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Genes & Development
|March 16, 2000
Summary
Wnt-1 induced secreted protein 1 (WISP-1) is a beta-catenin-regulated gene that promotes tumor formation. Its overexpression in cells transforms them and leads to tumor growth in mice.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Wnt-1 induced secreted protein 1 (WISP-1) is part of the CCN family of growth factors.
- The role of WISP-1 in tumorigenesis is under investigation.
Purpose of the Study:
- To identify WISP-1 as a beta-catenin-regulated gene.
- To investigate the role of WISP-1 in cancer development.
Main Methods:
- Cloning of the WISP-1 promoter.
- Analysis of WISP-1 transcriptional activation by Wnt-1 and beta-catenin.
- Overexpression of WISP-1 in normal rat kidney fibroblast cells (NRK-49F).
- Assessment of oncogenic activities including morphological transformation, cell growth, saturation density, anchorage-independent growth, and tumor formation in nude mice.
Main Results:
- WISP-1 promoter is activated by Wnt-1 and beta-catenin.
- CREB sites are important for WISP-1 transcriptional activation, while TCF/LEF sites play a minor role.
- WISP-1 overexpression induced morphological transformation, accelerated cell growth, and enhanced saturation density in NRK-49F cells.
- Overexpressed WISP-1 led to tumor formation in nude mice, despite lack of anchorage-independent growth.
Conclusions:
- WISP-1 is a beta-catenin-regulated gene contributing to tumorigenesis.
- WISP-1 exhibits oncogenic properties, promoting cell growth and tumor formation.
- Cellular attachment is crucial for WISP-1-mediated oncogenic signaling.