Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells.
Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells.
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DOI：
10.1186/1471-2407-7-111
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发表时间：
2007-06-28
期刊：
影响因子：
3.8
通讯作者：
Lin J
中科院分区：
文献类型：
--
作者：
Chen CL;Loy A;Cen L;Chan C;Hsieh FC;Cheng G;Wu B;Qualman SJ;Kunisada K;Yamauchi-Takihara K;Lin J
Stat3已被归类为原癌基因，组成型Stat3信号似乎与人类癌症的肿瘤发生有关。然而，组成型Stat3信号是否在骨肉瘤、横纹肌肉瘤和软组织肉瘤的存活和生长中起作用尚不清楚。为了检验Stat3是否在骨肉瘤、横纹肌肉瘤和其他软组织肉瘤中被激活，我们分别使用免疫组织化学和Western blot分析了肉瘤组织微阵列玻片和肉瘤细胞系，并使用了磷酸化特异性的Stat3抗体。为了研究激活的Stat3通路对肉瘤细胞生长和存活是否重要，腺病毒介导的显性阴性Stat3 （Y705F）和小分子抑制剂（称为STA-21）的表达被用于抑制表达Stat3磷酸化水平升高的人肉瘤细胞系中的组成型Stat3信号传导。MTT法测定细胞活力，western blotting法分析细胞凋亡诱导，使用特异性识别cleaved caspase -3、8和9的抗体。Stat3磷酸化在19%（21/113）的骨肉瘤、27%（17/64）的横纹肌肉瘤和15%（22/151）的其他软组织肉瘤组织以及肉瘤细胞系中升高。在表达磷酸化Stat3水平升高的人肉瘤细胞系中，显性阴性Stat3的表达和STA-21的处理通过caspase 3、8和9途径抑制细胞活力和生长，诱导细胞凋亡。本研究表明Stat3磷酸化在人横纹肌肉瘤、骨肉瘤和软组织肉瘤中升高。此外，Stat3通路的激活对于人肉瘤细胞的生长和存活非常重要。
Stat3 has been classified as a proto-oncogene and constitutive Stat3 signaling appears to be involved in oncogenesis of human cancers. However, whether constitutive Stat3 signaling plays a role in the survival and growth of osteosarcomas, rhabdomyosarcomas, and soft-tissue sarcomas is still unclear. To examine whether Stat3 is activated in osteosarcomas, rhabdomyosarcomas and other soft-tissue sarcomas we analyzed sarcoma tissue microarray slides and sarcoma cell lines using immunohistochemistry and Western blot analysis, respectively, with a phospho-specific Stat3 antibody. To examine whether the activated Stat3 pathway is important for sarcoma cell growth and survival, adenovirus-mediated expression of a dominant-negative Stat3 (Y705F) and a small molecule inhibitor (termed STA-21) were used to inhibit constitutive Stat3 signaling in human sarcoma cell lines expressing elevated levels of Stat3 phosphorylation. Cell viability was determined by MTT assays and induction of apoptosis was analyzed by western blotting using antibodies that specifically recognize cleaved caspases-3, 8, and 9. Stat3 phosphorylation is elevated in 19% (21/113) of osteosarcoma, 27% (17/64) of rhabdomyosarcoma, and 15% (22/151) of other soft-tissue sarcoma tissues as well as in sarcoma cell lines. Expression of the dominant-negative Stat3 and treatment of STA-21 inhibited cell viability and growth and induced apoptosis through caspases 3, 8 and 9 pathways in human sarcoma cell lines expressing elevated levels of phosphorylated Stat3. This study demonstrates that Stat3 phosphorylation is elevated in human rhabdomyosarcoma, osteosarcomas and soft-tissue sarcomas. Furthermore, the activated Stat3 pathway is important for cell growth and survival of human sarcoma cells.
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影响因子：
5.3
作者：
Bromberg, JF;Horvath, CM;Darnell, JE
通讯作者：
Darnell, JE
影响因子：
15.9
作者：
Levy, DE;Lee, CK
通讯作者：
Lee, CK
影响因子：
5.7
作者：
Lee, TL;Yeh, J;Chen, Z
通讯作者：
Chen, Z
影响因子：
37.8
作者：
Kunisada, K;Tone, E;Kishimoto, T
通讯作者：
Kishimoto, T
DOI：
10.1084/jem.20050730
发表时间：
2005-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nabarro S;Himoudi N;Papanastasiou A;Gilmour K;Gibson S;Sebire N;Thrasher A;Blundell MP;Hubank M;Canderan G;Anderson J
通讯作者：
Anderson J