Transforming growth factor-ß enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes

Paterson, I.C. and Davies, M. and Prime, S.S. and Eveson, J.W. and Price, N. and Ganapathy, A. and D’Mello, A. (2012) Transforming growth factor-ß enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes. International Journal of Experimental Pathology, 93. pp. 148-156. ISSN 0959-9673

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Abstract

Transforming growth factor-ß (TGF-ß) is known to act as a tumour suppressor early in carcinogenesis, but then switches to a pro-metastatic factor in some late stage cancers. However, the actions of TGF-ß are context dependent, and it is currently unclear how TGF-ß influences the progression of human squamous cell carcinoma(SCC). This study examined the effect of overexpression of TGF-ß1 or TGF-ß2 in Ras-transfected human malignant epidermal keratinocytes that represent the early stages of human SCC. In vitro, the proliferation of cells overexpressing TGF-ß1 or TGF-ß2 was inhibited by exogenous TGF-ß1; cells overexpressing TGF-ß1 also grew more slowly than controls, but the growth rate of TGF-ß2 overexpressing cells was unaltered. However, cells that overexpressed either TGF-ß1 or TGF-ß2 were markedly more invasive than controls in an organotypic model of SCC. The proliferation of the invading TGF-ß1 overexpressing cells in the organotypic assays was higher than controls. Similarly, tumours formed by the TGF-ß1 overexpressing cells following transplantation to athymic mice were larger than tumours formed by control cells and proliferated at a higher rate. Our results demonstrate that elevated expression of either TGF-ß1 or TGF-ß2 in cells that represent the early stages in the development of human SCC results in a more aggressive phenotype.

Item Type: Article
Additional Information: Dental Research and Training Unit and Oral Cancer Research Coordinating Centre, Faculty of Dentistry, University of Malaya---- doi: 10.1111/j.1365-2613.2011.00806.x
Uncontrolled Keywords: Invasion; isoform; keratinocytes; SCC; TGF-ß
Subjects: R Medicine > RK Dentistry
Divisions: Faculty of Dentistry
Depositing User: Ms. Izzan Ramizah Idris
Date Deposited: 23 Oct 2014 08:10
Last Modified: 23 Oct 2014 08:10
URI: http://eprints.um.edu.my/id/eprint/10107

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