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

Transforming growth factor- beta(TGF-beta) 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-beta are context dependent, and it is currently unclear how TGF-beta influences the progress...

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Main Authors: Davies, M., Prime, S.S., Eveson, J.W., Price, N., Ganapathy, A., D'Mello, A., Paterson, I.C.
Format: Article
Language:English
Published: Blackwell Publishing 2012
Subjects:
RK Dentistry
Online Access:http://eprints.um.edu.my/6035/1/Transforming_growth_factor-beta_enhances_invasion_and_metastasis_in_Ras-transfected_human_malignant_epidermal_keratinocytes.pdf
http://eprints.um.edu.my/6035/
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spelling my.um.eprints.60352013-05-08T01:36:12Z http://eprints.um.edu.my/6035/ Transforming growth factor-beta enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes Davies, M. Prime, S.S. Eveson, J.W. Price, N. Ganapathy, A. D'Mello, A. Paterson, I.C. RK Dentistry Transforming growth factor- beta(TGF-beta) 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-beta are context dependent, and it is currently unclear how TGF-beta influences the progression of human squamous cell carcinoma (SCC). This study examined the effect of overexpression of TGF-beta 1 or TGF-beta 2 in Ras-transfected human malignant epidermal keratinocytes that represent the early stages of human SCC. In vitro, the proliferation of cells overexpressing TGF-beta 1 or TGF-beta 2 was inhibited by exogenous TGF-beta 1; cells overexpressing TGF-beta 1 also grew more slowly than controls, but the growth rate of TGF-beta 2 overexpressing cells was unaltered. However, cells that overexpressed either TGF-beta 1 or TGF-beta 2 were markedly more invasive than controls in an organotypic model of SCC. The proliferation of the invading TGF-beta 1 overexpressing cells in the organotypic assays was higher than controls. Similarly, tumours formed by the TGF-beta 1 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-beta 1 or TGF-beta 2 in cells that represent the early stages in the development of human SCC results in a more aggressive phenotype. Blackwell Publishing 2012 Article PeerReviewed application/pdf en http://eprints.um.edu.my/6035/1/Transforming_growth_factor-beta_enhances_invasion_and_metastasis_in_Ras-transfected_human_malignant_epidermal_keratinocytes.pdf Davies, M. and Prime, S.S. and Eveson, J.W. and Price, N. and Ganapathy, A. and D'Mello, A. and Paterson, I.C. (2012) Transforming growth factor-beta enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes. International Journal of Experimental Pathology, 93 (2). pp. 148-156. ISSN 0959-9673 10.1111/j.1365-2613.2011.00806.x
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
language English
topic RK Dentistry
spellingShingle RK Dentistry
Davies, M.
Prime, S.S.
Eveson, J.W.
Price, N.
Ganapathy, A.
D'Mello, A.
Paterson, I.C.
Transforming growth factor-beta enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes
description Transforming growth factor- beta(TGF-beta) 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-beta are context dependent, and it is currently unclear how TGF-beta influences the progression of human squamous cell carcinoma (SCC). This study examined the effect of overexpression of TGF-beta 1 or TGF-beta 2 in Ras-transfected human malignant epidermal keratinocytes that represent the early stages of human SCC. In vitro, the proliferation of cells overexpressing TGF-beta 1 or TGF-beta 2 was inhibited by exogenous TGF-beta 1; cells overexpressing TGF-beta 1 also grew more slowly than controls, but the growth rate of TGF-beta 2 overexpressing cells was unaltered. However, cells that overexpressed either TGF-beta 1 or TGF-beta 2 were markedly more invasive than controls in an organotypic model of SCC. The proliferation of the invading TGF-beta 1 overexpressing cells in the organotypic assays was higher than controls. Similarly, tumours formed by the TGF-beta 1 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-beta 1 or TGF-beta 2 in cells that represent the early stages in the development of human SCC results in a more aggressive phenotype.
format Article
author Davies, M.
Prime, S.S.
Eveson, J.W.
Price, N.
Ganapathy, A.
D'Mello, A.
Paterson, I.C.
author_facet Davies, M.
Prime, S.S.
Eveson, J.W.
Price, N.
Ganapathy, A.
D'Mello, A.
Paterson, I.C.
author_sort Davies, M.
title Transforming growth factor-beta enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes
title_short Transforming growth factor-beta enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes
title_full Transforming growth factor-beta enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes
title_fullStr Transforming growth factor-beta enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes
title_full_unstemmed Transforming growth factor-beta enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes
title_sort transforming growth factor-beta enhances invasion and metastasis in ras-transfected human malignant epidermal keratinocytes
publisher Blackwell Publishing
publishDate 2012
url http://eprints.um.edu.my/6035/1/Transforming_growth_factor-beta_enhances_invasion_and_metastasis_in_Ras-transfected_human_malignant_epidermal_keratinocytes.pdf
http://eprints.um.edu.my/6035/
_version_ 1643687727693037568
score 13.211869

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