| Autor: |
van der Fits L; Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands., Qin Y, Out-Luiting JJ, Vermeer KG, Whittaker S, van Es JH, Tensen CP, Vermeer MH |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of investigative dermatology [J Invest Dermatol] 2012 Dec; Vol. 132 (12), pp. 2810-7. Date of Electronic Publication: 2012 Jun 21. |
| DOI: |
10.1038/jid.2012.203 |
| Abstrakt: |
NOTCH signaling is important for development and tissue homeostasis and is activated in many human cancers. We investigated a role for NOTCH1 signaling in Sézary syndrome (SS), a cutaneous T-cell lymphoma in which CD4+ tumor cells (Sézary cells) are present in the skin, lymph nodes, and peripheral blood. We show consistent expression of activated NOTCH1 by Sézary cells isolated from peripheral blood of SS patients, as well as the SS-derived cell lines SeAx and HuT78. In addition, immunohistochemical stainings of skin biopsies from SS patients showed consistent expression of nuclear NOTCH1 and its downstream target hairy/enhancer of split-1 (HES1) by Sézary cells. We demonstrate that this persistent NOTCH1 activation is not caused by mutations in the coding regions of NOTCH1 and F-box and WD40 domain protein 7 (FBWX7) genes. Inhibition of NOTCH1 signaling by gamma secretase inhibitors decreased cellular viability and induced apoptosis of Sézary cells. These observations argue that NOTCH1 signaling is functionally involved in the pathogenesis of SS, and inhibition of NOTCH1 signaling represents a new therapeutic target for the treatment of SS. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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