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

Agochiya, M., Brunton, V.G., Owens, D.W., Parkinson, E.K., Paraskeva, C., Keith, W.N. and Frame, M.C. (1999) Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells. Oncogene, 18(41), pp. 5646-5653.

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Publisher's URL: http://www.nature.com/onc/journal/v18/n41/index.html

Abstract

Focal adhesion kinase (pp125<sup><font size="-1">FAK</font></sup>) 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, pp125<sup><font size="-1">FAK</font></sup> is involved in cellular processes such as spreading, motility, growth and survival. In addition, a number of reports have indicated that pp125<sup><font size="-1">FAK</font></sup> may be up-regulated in human tumour cells of diverse origin, and consequently, a role has been proposed for pp125<sup><font size="-1">FAK</font></sup> in the development of invasive cancers. However, to date the mechanisms that lead to elevated pp125<sup><font size="-1">FAK</font></sup> expression in tumour cells have not been determined. Here we used <i><b>in situ</b></i> hybridization to confirm chromosome 8q as the genomic location of the human <i><b>fak</b></i> gene and report that elevation of pp125<sup><font size="-1">FAK</font></sup> protein in cell lines derived from invasive squamous cell carcinomas is accompanied by gains in copy number of the <i><b>fak</b></i> gene in all cases examined. In addition, we observed increased <i><b>fak</b></i> copy number in frozen sections of squamous cell carcinomas. Furthermore, increased dosage of the <i><b>fak</b></i> 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 <i><b>fak</b></i> was amplified. In addition, in an <i><b>in vitro</b></i> model for human colon cancer progression there was a copy number gain of the <i><b>fak</b></i> gene during conversion from adenoma to carcinoma, which was associated with increased pp125<sup><font size="-1">FAK</font></sup> protein expression. Thus, we show for the first time that many cell lines derived from invasive epithelial tumours have increased dosage of the <i><b>fak</b></i> gene, which may contribute to the elevated protein expression commonly observed. Although other genes near the <i><b>fak</b></i> locus are co-amplified or increased in copy number, including the proto-oncogene c-<i><b>myc</b></i>, the biological properties of pp125<sup><font size="-1">FAK</font></sup> 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Keith, Professor Nicol
Authors: Agochiya, M., Brunton, V.G., Owens, D.W., Parkinson, E.K., Paraskeva, C., Keith, W.N., and Frame, M.C.
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Q Science > QH Natural history > QH426 Genetics
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncogene
ISSN:0950-9232

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