Identification of a Stat3-dependent transcription regulatory network involved in metastatic progression.
Identification of a Stat3-dependent transcription regulatory network involved in metastatic progression.
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DOI：
10.1158/0008-5472.can-09-1684
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发表时间：
2009-09-01
期刊：
影响因子：
11.2
通讯作者：
Muller WJ
中科院分区：
文献类型：
--
作者：
Ranger JJ;Levy DE;Shahalizadeh S;Hallett M;Muller WJ
高水平的活化Stat3经常在人类乳腺癌中发现，并与患者预后不良相关。我们采用激活erbb2的乳腺癌小鼠模型来研究Stat3在乳腺肿瘤进展中的体内作用，发现Stat3不会改变乳腺肿瘤的发生，但会显著影响转移进展。与野生型队列的肿瘤相比，在缺乏Stat3的情况下，肺转移的动物减少了4倍，而在Stat3缺失的肿瘤中，肺病变数量减少了12倍。stat3缺陷肿瘤的恶性肿瘤减少归因于与stat3依赖的C/EBPδ转录级联相关的血管生成和炎症反应的减少。
High levels of activated Stat3 are often found in human breast cancers and can correlate with poor patient outcome. We employed an activated-ErbB2 mouse model of breast cancer to investigate the in vivo role of Stat3 in mammary tumor progression and found that Stat3 does not alter mammary tumor initiation but dramatically affects metastatic progression. Four-fold fewer animals exhibited lung metastases in the absence of Stat3 and a 12-fold reduction in the number of lung lesions was observed in the Stat3-null tumors when compared to tumors from the wild type cohort. The decreased malignancy in Stat3-deficient tumors is attributed to a reduction in both angiogenic and inflammatory responses associated with a Stat3-dependent transcriptional cascade involving C/EBPδ.