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Bispebjerg Hospital - a part of Copenhagen University Hospital
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Ubiquitin-specific protease 2 decreases p53-dependent apoptosis in cutaneous T-cell lymphoma

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  1. Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome

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  2. Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma

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  1. Photochemotherapy Induces Interferon Type III Expression via STING Pathway

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  2. Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin

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  3. Branched evolution and genomic intratumor heterogeneity in the pathogenesis of cutaneous T-cell lymphoma

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  4. Overall Survival in Mycosis Fungoides: A Systematic Review and Meta-Analysis

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Treatment of advanced cutaneous T-cell lymphomas (CTCL) is challenging because they are resistant to conventional chemotherapy. USP2 has been shown to promote resistance to chemotherapeutic agents in several cancer models.We show here USP2 is expressed in quiescent and activated T-cells and its expression is 50% lower in CTCL cell lines (MyLa2000, SeAx and Hut-78) than in normal T-cells. USP2 is expressed in neoplastic cells in early, plaque-stage mycosis fungoides (MF) and is downregulated in advanced tumor stages. Upon treatment with psoralen with UVA (PUVA) or a p53 activator, nutlin3a, USP2 expression is significantly increased in MyLa2000 (p53wt/wt), but not in SeAx (p53mut) or Hut-78 (p53-/-). USP2 knockdown decreases MyLa2000 cell viability after PUVA by 50% but not Hut-78, suggesting that the function of USP2 in CTCL cells is p53-dependent. Furthermore, USP2 knockdown results in a decreased Mdm2 expression and upregulation of p53. Taken together, our findings suggest that USP2 stabilizes Mdm2 which antagonizes pro-apoptotic activity of p53 and possibly contributes to therapeutic resistance in CTCL.

Original languageEnglish
JournalOncotarget
Volume7
Issue number30
Pages (from-to)48391-48400
Number of pages10
ISSN1949-2553
DOIs
Publication statusPublished - 26 Jul 2016

ID: 49766861