Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer.
Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer.
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DOI：
10.1186/bcr1680
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Bromberg JF
中科院分区：
文献类型：
--
作者：
Berishaj M;Gao SP;Ahmed S;Leslie K;Al-Ahmadie H;Gerald WL;Bornmann W;Bromberg JF
信号转导子和转录激活子3（Stat 3）在大约50%的原发性乳腺癌中组成性酪氨酸磷酸化。许多不同的机制负责Stat 3激活，包括受体酪氨酸激酶，Src和Janus激酶（Jaks）的异常激活，已被牵连在乳腺癌。我们检查了6个乳腺癌来源的细胞系表达高或低水平的酪氨酸磷酸化Stat 3（pStat 3）以及原发性乳腺癌标本。Src或EGFR（表皮生长因子受体）酪氨酸激酶的抑制对pStat 3水平没有影响，而pan-Jak抑制剂P6导致Stat 3磷酸化的完全废除和生长抑制。Jaks是细胞因子信号传导所必需的，并且糖蛋白130（gp 130）受体相关的Jaks是Stat 3磷酸化的已知介质。gp 130受体的阻断或白细胞介素-6（IL-6）配体的螯合导致pStat 3水平的降低。来自表达高水平pStat 3的那些细胞系的条件培养基含有IL-6并且能够刺激Stat 3磷酸化。我们检测了原发性乳腺肿瘤中的IL-6水平，发现pStat 3和IL-6表达之间呈正相关。总之，乳腺癌中Stat 3活化的主要机制是通过IL-6/gp 130/Jak途径。
Signal transducer and activator of transcription 3 (Stat3) is constitutively tyrosine-phosphorylated in approximately 50% of primary breast carcinomas. A number of different mechanisms responsible for Stat3 activation, including abnormal activation of receptor tyrosine kinases, Src, and Janus kinases (Jaks), have been implicated in breast cancer. We examined six breast cancer-derived cell lines expressing high or low levels of tyrosine-phosphorylated Stat3 (pStat3) as well as primary breast cancer specimens. Inhibition of Src or EGFR (epidermal growth factor receptor) tyrosine kinases had no effect on pStat3 levels, whereas pan-Jak inhibitor P6 resulted in complete abrogation of Stat3 phosphorylation and inhibition of growth. Jaks are required for cytokine signaling, and the glycoprotein 130 (gp130) receptor-associated Jaks are known mediators of Stat3 phosphorylation. Blockade of the gp130 receptor or sequestration of the interleukin-6 (IL-6) ligand led to a decrease of pStat3 levels. Conditioned media from those cell lines expressing high levels of pStat3 contained IL-6 and were capable of stimulating Stat3 phosphorylation. We examined IL-6 levels in primary breast tumors and found a positive correlation between pStat3 and IL-6 expression. In summary, a principal mechanism of Stat3 activation in breast cancer is through the IL-6/gp130/Jak pathway.
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影响因子：
11.2
作者：
Leslie, K;Lang, C;Bromberg, J
通讯作者：
Bromberg, J
DOI：
10.1073/pnas.0404100101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Dechow, TN;Pedranzini, L;Bromberg, JF
通讯作者：
Bromberg, JF
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
15.9
作者：
Bromberg, J
通讯作者：
Bromberg, J
影响因子：
11.5
作者：
Diaz, N;Minton, S;Muro-Cacho, CA
通讯作者：
Muro-Cacho, CA