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,
![[img]](http://eprints.um.edu.my/style/images/fileicons/application_pdf.png) |
PDF
Transforming_growth_factor-b_enhances_invasion_and_metastasis.pdf - Published Version Restricted to Repository staff only Download (571kB) | Request a copy |
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 |
|---|---|
| Funders: | UNSPECIFIED |
| 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 |
Actions (login required)
 |
View Item |
