Scott, L., Vass, J., Parkinson, E., Gillespie, D., Winnie, J. and Ozanne, B. (2004) Invasion of normal human fibroblasts induced by v-Fos is independent of proliferation, immortalization, and the tumor suppressors p16 (INK4a) and p53. Molecular and Cellular Biology, 24(4), pp. 1540-1559. (doi: 10.1128/MCB.24.4.1540-1559.2004)
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Abstract
Invasion is generally perceived to be a late event during the progression of human cancer, but to date there are no consistent reports of alterations specifically associated with malignant conversion. We provide evidence that the v-Fos oncogene induces changes in gene expression that render noninvasive normal human diploid fibroblasts highly invasive, without inducing changes in growth factor requirements or anchorage dependence for proliferation. Furthermore, v-Fos-stimulated invasion is independent of the pRb/p16(INK4a) and p53 tumor suppressor pathways and telomerase. We have performed microarray analysis using Affymetrix GeneChips, and the gene expression profile of v-Fos transformed cells supports its role in the regulation of invasion, independent from proliferation. We also demonstrate that invasion, but not proliferation, is dependent on the activity of the up-regulated epidermal growth factor receptor. Taken together, these results indicate that AP-1-directed invasion could precede deregulated proliferation during tumorigenesis and that sustained activation of AP-1 could be the epigenetic event required for conversion of a benign tumor into a malignant one, thereby explaining why many malignant human tumors present without an obvious premalignant hyperproliferative dysplastic lesion.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Gillespie, Professor David and Ozanne, Professor Bradford |
Authors: | Scott, L., Vass, J., Parkinson, E., Gillespie, D., Winnie, J., and Ozanne, B. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Molecular and Cellular Biology |
ISSN: | 0270-7306 |
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