Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma

Autor: Yvonne Remache, Andre Goy, Panagiota Tsioli, Kevin B. Spurgers, Frederic Gilles, L. Jeffrey Medeiros, Georgios Z. Rassidakis, Hesham M. Amin, Jeong Hee Cho-Vega, Francisco Vega
Rok vydání: 2004
Předmět:
STAT3 Transcription Factor
Cancer Research
Suppressor of Cytokine Signaling Proteins
Biology
hemic and lymphatic diseases
medicine
Tumor Cells
Cultured
Anaplastic lymphoma kinase
Humans
Immunoprecipitation
Anaplastic Lymphoma Kinase
SOCS3
Phosphorylation
Anaplastic large-cell lymphoma
Oligonucleotide Array Sequence Analysis
Janus kinase 3
Large cell
Gene Expression Profiling
digestive
oral
and skin physiology
Janus Kinase 3
Receptor Protein-Tyrosine Kinases
Hematology
Protein-Tyrosine Kinases
medicine.disease
Lymphoma
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
Repressor Proteins
Alternative Splicing
Oncology
Suppressor of Cytokine Signaling 3 Protein
Mutation
Cancer research
STAT protein
Quinazolines
Trans-Activators
Lymphoma
Large-Cell
Anaplastic
Signal Transduction
Transcription Factors
Zdroj: Leukemia. 18(11)
ISSN: 0887-6924
Popis: Using a cDNA microarray, we found that suppressor of cytokine signaling 3 (SOCS3) is highly expressed in anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphoma (ALCL) cell lines. As SOCS3 is induced by activated signal transducer and activator of transcription 3 (STAT3), and ALK activates STAT3, we hypothesized that SOCS3 may play a role in ALK+ ALCL pathogenesis via the Janus kinase 3 (JAK3)-STAT3 pathway. Using ALCL cell lines, we show by coimmunoprecipitation experiments that SOCS3 physically binds with JAK3 in vitro, and that JAK3 inhibition by WHI-P154 downregulates SOCS3 expression. Western blot analysis confirmed expression of SOCS3 and also showed coexpression of phosphorylated (activated) STAT3 (pSTAT3). Direct sequencing of the SOCS3 gene showed no mutations or alternative splicing. In ALCL tumors that were assessed by immunohistochemistry, nine of 12 (75%) ALK+ tumors were SOCS3 positive and eight (67%) coexpressed pSTAT3. In comparison, 18 of 25 (72%) ALK-- tumors were SOCS3 positive and seven (28%) coexpressed pSTAT3. These results show that SOCS3 is overexpressed in ALCL, attributable to JAK3-STAT3 activation and likely related to ALK in ALK+ tumors. However, SOCS3 is also expressed in tumors that lack STAT3 and ALK suggesting alternative mechanisms of upregulation.
Databáze: OpenAIRE
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