c-CBL E3 Ubiquitin Ligase Expression Increases Across the Spectrum of Benign and Malignant T-Cell Skin Diseases.
Prolonged survival of lesional T cells plays a central role in the pathogenesis of T-cell-mediated dermatoses. We have recently shown that the ubiquitin ligase c-CBL is highly expressed in cutaneous T-cell lymphoma (CTCL) and that its knockdown increases activation-induced cell death, a key pathway for T-cell apoptosis. Here, we extend our work on c-CBL expression in malignant T cells to their nonneoplastic counterparts in benign inflammatory dermatoses. Immunohistochemical staining with anti-c-CBL antibody was performed on lesional biopsies from a total of 65 patients with atopic dermatitis, allergic contact dermatitis, pityriasis rosea, psoriasis vulgaris, lichen planus, mycosis fungoides (MF)/Sézary syndrome (SS) as well as on tonsil tissue from 5 individuals and on 5 human CTCL cell lines. Protein levels were measured in situ using multispectral image analysis, a quantitative method that is ×5 more sensitive than standard immunohistology for antigen detection. There was a significant (P < 0.05) and progressive increase of mean c-CBL expression across the spectrum of inflammatory dermatoses (2-fold), MF/SS (3-fold), and lymphoma cell lines (4-fold) as compared with tonsillar T lymphocytes. A subset of MF/SS cases expressed mean c-CBL levels above the ranges observed in inflammatory dermatoses. Given our prior finding that c-CBL inhibits activation-induced cell death, c-CBL might play a role in the pathogenesis of inflammatory dermatoses and CTCL.
*Department of Dermatology, University of Wisconsin, Madison, WI; and †Department of Dermatology, William S. Middleton VA Medical Center, Madison, WI.
Katrin A
KA
Salva
Margo J
MJ
Reeder
Rita
R
Lloyd
Gary S
GS
Wood
D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000201:enzymology* / Q000473:pathology; D050721:Proto-Oncogene Proteins c-cbl / Q000032:analysis / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology
D014408:Biomarkers, Tumor; D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human