STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma
STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma
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DOI：
10.1182/blood.v97.4.1056
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发表时间：
2001-02-15
期刊：
影响因子：
20.3
通讯作者：
Odum, N
中科院分区：
文献类型：
--
作者：
Brender, C;Nielsen, M;Odum, N
肿瘤转化的一个特征是细胞因子和细胞外基质对细胞分化、迁移和有丝分裂的外部控制丧失。由于细胞因子信号传导抑制因子（SOCS）蛋白是精氨酸诱导的信号传导的负调节因子，因此假设异常的SOCS表达在肿瘤转化中起作用。本研究报告了皮肤T细胞淋巴瘤（CTCL）细胞系中的组成性SOCS-3表达。SOCS-3蛋白质在肿瘤细胞系（但非恶性T细胞）中组成型表达，所述肿瘤细胞系获自蕈样肉芽肿（MF）患者的受影响皮肤和Sezary综合征（SS）患者的外周血。相反，在白血病Jurkat T细胞系、MOLT-4急性淋巴细胞白血病细胞系和单核细胞白血病细胞系U937中未发现组成型SOCS-3表达。SOCS-3的表达与STATE在CTCL肿瘤细胞中的组成性激活相一致，并且具有显性负性STATE的CTCL肿瘤细胞的稳定转染强烈抑制SOCS-3表达，而野生型STAT 3的转染则不会。此外，用显性负性STAT 3转染的细胞中SOCS-3表达的降低与对干扰素-α（IFN-α）的敏感性增加相关。总之，证据提供了一个组成型SOCS-3表达的癌细胞从CTCL患者。此外，研究结果表明，SOCS-3的异常表达是由CTCL细胞中STATE的组成性激活介导的，并影响这些细胞的IFN-α敏感性。(C)2001年，美国血液学会。
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 STATE in CTCL tumor cells, and stable transfection of CTCL tumor cells with a dominant negative STATE strongly inhibits SOCS-3 expression, whereas transfection with wildtype 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 indicate that the aberrant expression of SOCS-3 is mediated by a constitutive activation of STATE in CTCL cells and affects the IFN-alpha sensitivity of these cells. (C) 2001 by The American Society of Hematology.