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Ubiquitin-specific protease 2 decreases p53-dependent apoptosis in cutaneous T-cell lymphoma.
- Source :
-
Oncotarget [Oncotarget] 2016 Jul 26; Vol. 7 (30), pp. 48391-48400. - Publication Year :
- 2016
-
Abstract
- 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.<br />Competing Interests: No conflicts of interest.
- Subjects :
- Aged
Aged, 80 and over
Apoptosis physiology
Cell Line, Tumor
Endopeptidases genetics
Female
Humans
Lymphoma, T-Cell, Cutaneous genetics
Lymphoma, T-Cell, Cutaneous pathology
Male
Middle Aged
Skin Neoplasms pathology
Tumor Suppressor Protein p53 genetics
Ubiquitin Thiolesterase
Endopeptidases metabolism
Lymphoma, T-Cell, Cutaneous metabolism
Skin Neoplasms genetics
Skin Neoplasms metabolism
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 30
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27351221
- Full Text :
- https://doi.org/10.18632/oncotarget.10268