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Functional and prog...
Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma
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Gremel, G. (author)
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Ryan, D. (author)
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Rafferty, M. (author)
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Lanigan, F. (author)
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Hegarty, S. (author)
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Lavelle, M. (author)
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Murphy, I. (author)
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Unwin, L. (author)
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Joyce, C. (author)
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Faller, W. (author)
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McDermott, E. W. (author)
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Sheahan, K. (author)
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- Pontén, Fredrik (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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Gallagher, W. M. (author)
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(creator_code:org_t)
- 2011-07-05
- 2011
- English.
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 105:4, s. 565-574
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- BACKGROUND: The homeobox containing transcription factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer. METHODS: Using a selection of two-and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used. RESULTS: Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P = 0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity. CONCLUSIONS: MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.
Keyword
- melanoma
- MSX2
- homeobox
- apoptosis
- spheroid invasion
- biomarker
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Gremel, G.
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Ryan, D.
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Rafferty, M.
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Lanigan, F.
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Hegarty, S.
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Lavelle, M.
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show more...
-
Murphy, I.
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Unwin, L.
-
Joyce, C.
-
Faller, W.
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McDermott, E. W.
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Sheahan, K.
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Pontén, Fredrik
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Gallagher, W. M.
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show less...
- Articles in the publication
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British Journal ...
- By the university
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Uppsala University