The Wnt/β-catenin signal transduction pathway plays a central role in metazoan development, controlling such diverse processes as cell growth, proliferation and organogenesis. Wnt-1 was initially identified as a mammary oncogene. Mutations in other components of this signal transduction pathway - APC, β-catenin and Axin - have been implicated in the initiation and progression of an increasing number of human malignancies. Aberrant activation of this pathway leads to the inappropriate expression of target genes such as c-MYC and CYCLIN D1. Elucidation of additional target genes of this pathway will shed further light upon the mechanisms underlying the malignant phenotype. As an in vitro model of Wnt/β-catenin signalling in the mouse mammary gland, mammary epithelial cell lines were generated in which this pathway could be activated in a tetracycline-dependent manner. The transcriptional consequences of aberrant Wnt/β-catenin signalling were then investigated using cDNA microarrays. Using this approach, 70 genes have been identified as being potential transcriptionally upregulated targets of the pathway and a similar number have been shown to be repressed. Similar experiments were performed in a colorectal cancer cell line lacking functional APC. An analysis of a representative sample of these differentially expressed genes is presented here. The use of human tumour tissue microarrays containing 300 tumour samples from a variety of tissues was validated as an approach to test the relevance of candidate genes.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:541291 |
| Date | January 2002 |
| Creators | Kenny, Paraic A. |
| Publisher | Institute of Cancer Research (University Of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://publications.icr.ac.uk/9712/ |
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