STAT3 activation abrogates growth factor dependence and contributes to head and neck squamous cell carcinoma tumor growth in vivo.
STAT3 activation abrogates growth factor dependence and contributes to head and neck squamous cell carcinoma tumor growth in vivo.
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发表时间：
2002-08
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通讯作者：
T. Kijima;H. Niwa;R. Steinman;S. D. Drenning;W. Gooding;Abbey L. Wentzel;S. Xi;J. Grandis
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作者：
T. Kijima;H. Niwa;R. Steinman;S. D. Drenning;W. Gooding;Abbey L. Wentzel;S. Xi;J. Grandis
表皮生长因子受体（EGFR）上调，导致头颈部鳞状细胞癌（SCCHN）生长失控。以前，我们报道了自分泌刺激EGFR和组成性信号转导和转录激活因子（STAT）3在SCCHN细胞在体外和体内激活之间的关联。在这里，我们评估了活化的STAT 3在肿瘤进展和EGFR非依赖性促有丝分裂信号传导中的作用。我们发现，稳定转染显性活性STAT 3构建体的SCCHN细胞表达了升高水平的STAT 3靶基因，包括Bcl-X（L）和细胞周期蛋白D1，并表现出体外增殖增加和体内肿瘤生长速度更快。细胞周期分析表明G2-M中STAT 3构建体转染子的比例增加。这些发现提供了证据表明，组成性STAT 3激活有助于SCCHN中的肿瘤生长，独立于EGFR自分泌轴。
Epidermal growth factor receptor (EGFR) is up-regulated and contributes to the loss of growth control in squamous cell carcinoma of the head and neck (SCCHN). Previously, we reported an association between autocrine stimulation of EGFR and constitutive signal transducers and activators of transcription (STAT) 3 activation in SCCHN cells in vitro and in vivo. Here, we evaluated the role of activated STAT3 in tumor progression and EGFR-independent mitogenic signaling. We found that SCCHN cells stably transfected with a dominant active STAT3 construct expressed elevated levels of STAT3 target genes, including Bcl-X(L) and cyclin D1, and demonstrated increased proliferation in vitro and more rapid tumor growth rates in vivo. Cell cycle analysis demonstrated an increased proportion of STAT3 construct transfectants in G(2)-M. These findings provide evidence that constitutive STAT3 activation contributes to tumor growth in SCCHN, independent of the EGFR autocrine axis.