Cited by 129Cutaneous lymphoproliferative disorders researchCytokine Signaling Pathways and InteractionsProtein Tyrosine Phosphatases

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STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma

Brender, Christine, Nielsen, Mette, Kaltoft, Keld, Mikkelsen, Gitte, Zhang, Qian, Wasik, Mariusz, Billestrup, Nils, Ødum, Niels·2001·Blood

DOI 10.1182/blood.v97.4.1056

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Abstract

A characteristic feature of neoplastic transformation is the loss of external control by cytokines and extracellular matrix of cellular differentiation, migration, and mitogenesis. Because suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine-induced signaling, it has been hypothesized that an aberrant SOCS expression plays a role in neoplastic transformation. This study reports on a constitutive SOCS-3 expression in cutaneous T-cell lymphoma (CTCL) cell lines. SOCS-3 protein is constitutively expressed in tumor cell lines (but not in nonmalignant T cells) obtained from affected skin from a patient with mycosis fungoides (MF) and from peripheral blood from a patient with Sezary syndrome (SS). In contrast, constitutive SOCS-3 expression is not found in the leukemic Jurkat T-cell line, the MOLT-4 acute lymphoblastic leukemia cell line, and the monocytic leukemic cell line U937. Expression of SOCS-3 coincides with a constitutive activation of STAT3 in CTCL tumor cells, and stable transfection of CTCL tumor cells with a dominant negative STAT3 strongly inhibits SOCS-3 expression, whereas transfection with wild-type STAT3 does not. Moreover, the reduced SOCS-3 expression in cells transfected with the dominant negative STAT3 is associated with an increased sensitivity to interferon-alpha (IFN-alpha). In conclusion, evidence is provided for a constitutive SOCS-3 expression in cancer cells obtained from patients with CTCL. Moreover, the findings indica…

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Authors: Brender, C., Nielsen, M., Kaltoft, K., Mikkelsen, G., Zhang, Q., Wasik, M., Billestrup, N., & Ødum, N.
Affiliations: University of Copenhagen (DK)
ORCID: Zhang, Qian
Wasik, Mariusz
Billestrup, Nils
Ødum, Niels
Venue: Blood
Publisher: American Society of Hematology
Published: 2001-02-15
Volume: 97
Issue: 4
Pages: 1056-1062
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood.v97.4.1056
OpenAlex: W2020666846
Cited by: 129
References: 40
Citations by year: 2024: 1 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 11
FWCI: 11.56
Type: journal article
Language: en
Open access: closed
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: National Cancer Institute (CA 89194, R01CA089194)
Topics: Health Sciences › Medicine › Dermatology › Cutaneous lymphoproliferative disorders research
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords: SOCS3, STAT3, cutaneous T-cell lymphoma, mycosis fungoides, Sézary syndrome, constitutive expression, dominant-negative STAT3, suppressor of cytokine signaling, oncogenic transformation, cytokine signaling
MeSH terms: Suppressor of Cytokine Signaling 3 Protein, Cell Transformation, Neoplastic, Dimethyl Sulfoxide, DNA-Binding Proteins, Enzyme Inhibitors, Genes, Dominant, Humans, Interferon-gamma, Mutation, Mycosis Fungoides, Neoplasm Proteins, Proteins, Quinazolines, Recombinant Fusion Proteins, Repressor Proteins, RNA, Messenger, RNA, Neoplasm, Sezary Syndrome, Skin Neoplasms, Transcription Factors, Transcription, Genetic, Transfection, Protein Biosynthesis, Tumor Cells, Cultured, Leukemia-Lymphoma, Adult T-Cell, Trans-Activators, Gene Expression Regulation, Neoplastic, Interferon-alpha, Jurkat Cells, Tyrphostins, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins

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STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma

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