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  • Original Paper
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Regulation of a multigenic invasion programme by the transcription factor, AP-1: re-expression of a down-regulated gene, TSC-36, inhibits invasion

Oncogene volume 19, pages 5348–5358 (2000)Cite this article

Abstract

The transcription factor AP-1 (activator protein-1) is required for transformation by many oncogenes, which function upstream of it in the growth factor-ras signal transduction pathway. Previously, we proposed that one role of AP-1 in transformation is to regulate the expression of a multigenic invasion programme. As a test of this proposal we sought to identify AP-1 regulated genes based upon their differential expression in 208F rat fibroblasts transformed by FBR-v-fos (FBR), and to determine if they functioned in the invasion programme. Subtracted cDNA libraries specific for up- or down-regulated genes in FBRs compared to 208Fs were constructed and analysed. Northern analysis revealed that the cDNAs in both libraries represented differentially expressed genes. Nucleic acid sequence analysis of randomly selected cDNA clones from each library coupled with searches of nucleic acid and amino acid sequence databases determined that many of the cDNAs represented proteins that function in various aspects of the invasion process. Functional analysis of one the down-regulated genes, TSC-36/follistatin-related protein (TSC-36/Frp), which has not previously been associated with invasion, demonstrated that its expression in FBRs inhibited in vitro invasion. These results support the proposal that AP-1 in transformed cells regulates a multigenic invasion programme.

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Acknowledgements

We thank Professor JA Wyke for his helpful criticisms. This work was supported by The Cancer Research Campaign and The Beatson Institute for Cancer Research. IMPJ was the recipient of a Medical Research Council studentship.

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  1. Beatson Institute for Cancer Research, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD

    Imogen MP Johnston, Heather J Spence, Joseph N Winnie, Lynn McGarry, J Keith Vass, Liam Meagher, Genevieve Stapleton & Bradford W Ozanne

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Johnston, I., Spence, H., Winnie, J. et al. Regulation of a multigenic invasion programme by the transcription factor, AP-1: re-expression of a down-regulated gene, TSC-36, inhibits invasion. Oncogene 19, 5348–5358 (2000). https://doi.org/10.1038/sj.onc.1203927

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