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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| Format: | Article |
| Language: | English |
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Blackwell Publishing
2012
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| 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 |
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| 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. |
| collection | UM |
| 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. |
| first_indexed | 2024-03-06T05:15:48Z |
| format | Article |
| id | um.eprints-6035 |
| institution | Universiti Malaya |
| language | English |
| last_indexed | 2024-03-06T05:15:48Z |
| publishDate | 2012 |
| publisher | Blackwell Publishing |
| record_format | dspace |
| spelling | 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, DOI https://doi.org/10.1111/j.1365-2613.2011.00806.x <https://doi.org/10.1111/j.1365-2613.2011.00806.x>. 10.1111/j.1365-2613.2011.00806.x |
| 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 |
| title | 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_short | 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 |
| topic | RK Dentistry |
| url | http://eprints.um.edu.my/6035/1/Transforming_growth_factor-beta_enhances_invasion_and_metastasis_in_Ras-transfected_human_malignant_epidermal_keratinocytes.pdf |
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