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Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells

Oncogene volume 18, pages 5646–5653 (1999)Cite this article

Abstract

Focal adhesion kinase (pp125FAK) is present at sites of cell/extracellular matrix adhesion and has been implicated in the control of cell behaviour. In particular, as a key component of integrin-stimulated signal transduction pathways, pp125FAK is involved in cellular processes such as spreading, motility, growth and survival. In addition, a number of reports have indicated that pp125FAK may be up-regulated in human tumour cells of diverse origin, and consequently, a role has been proposed for pp125FAK in the development of invasive cancers. However, to date the mechanisms that lead to elevated pp125FAK expression in tumour cells have not been determined. Here we used in situ hybridization to confirm chromosome 8q as the genomic location of the human fak gene and report that elevation of pp125FAK protein in cell lines derived from invasive squamous cell carcinomas is accompanied by gains in copy number of the fak gene in all cases examined. In addition, we observed increased fak copy number in frozen sections of squamous cell carcinomas. Furthermore, increased dosage of the fak gene was also observed in many cell lines derived from human tumours of lung, breast and colon, including two cell lines Calu3 and HT29, in which fak was amplified. In addition, in an in vitro model for human colon cancer progression there was a copy number gain of the fak gene during conversion from adenoma to carcinoma, which was associated with increased pp125FAK protein expression. Thus, we show for the first time that many cell lines derived from invasive epithelial tumours have increased dosage of the fak gene, which may contribute to the elevated protein expression commonly observed. Although other genes near the fak locus are co-amplified or increased in copy number, including the proto-oncogene c-myc, the biological properties of pp125FAK in controlling the growth, survival and invasiveness of tumour cells, suggest that it may contribute to the selection pressure for maintaining increased dosage of the region of chromosome 8q that encodes these genes.

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Acknowledgements

We thank Adam Hurlstone for his help with PAC isolation, members of Nicol Keith's lab for help with FISH analysis, David Gillespie for the anti-c-Myc antibody, Alan Richardson and Tom Parsons for pp125FAK cDNA and John Wyke for reading the manuscript. This work was supported by the Cancer Research Campaign (UK). V Brunton and D Owens were supported by the Medical Research Council (UK).

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Authors and Affiliations

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

    Mahima Agochiya, Valerie G Brunton, Dewi W Owens, E Kenneth Parkinson & Margaret C Frame

  2. Department of Pathology and Microbiology, University of Bristol, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK

    Christos Paraskeva

  3. Glasgow University Department of Medical Oncology, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK

    W Nicol Keith

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  1. Mahima Agochiya
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  2. Valerie G Brunton
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Agochiya, M., Brunton, V., Owens, D. et al. Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells. Oncogene 18, 5646–5653 (1999). https://doi.org/10.1038/sj.onc.1202957

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