Yale University School of Medicine Section of Otolaryngology, 333 Cedar St, Box 208041, New Haven, Connecticut 06520, USA.
Head Neck. 2011 Nov;33(11):1586-99. doi: 10.1002/hed.21648. Epub 2010 Dec 28.
Activating transcription factor-2 (ATF2) is associated with tumor progression but is not well studied in head and neck squamous cell carcinoma (HNSCC). Its effects in stress and its importance in other survival mechanisms were studied.
ATF2 expression and nuclear activation were confirmed in HNSCC. After modulation of ATF2, in vitro effects on proliferation and chemosensitivity were studied. Effects on in vivo tumor growth and interleukin 8 (IL-8) expression were determined. Tumor necrosis factor-alpha (TNF-α) treatment was used to further evaluate cytokine production and chemosensitivity.
Reductions of ATF2 resulted in significant nuclear p-ATF2 activation, cisplatin resistance, and augmented IL-8 expression without affecting in vivo tumor growth. In this setting, TNF increases p-p38 phosphorylation and chemosensitivity while further enhancing IL-8 production.
Our data suggest regulatory roles for ATF2 in TNF-related mechanisms of HNSCC. Its perturbation and nuclear activation are associated with significant effects on survival and cytokine production.
激活转录因子 2（ATF2）与肿瘤进展相关，但在头颈部鳞状细胞癌（HNSCC）中的研究并不充分。本研究旨在研究其在应激中的作用及其在其他生存机制中的重要性。
在 HNSCC 中证实了 ATF2 的表达和核激活。在调节 ATF2 后，研究了其对体外增殖和化疗敏感性的影响。还测定了对体内肿瘤生长和白细胞介素 8（IL-8）表达的影响。使用肿瘤坏死因子-α（TNF-α）治疗来进一步评估细胞因子产生和化疗敏感性。
ATF2 的减少导致显著的核 p-ATF2 激活、顺铂耐药和 IL-8 表达增加，但不影响体内肿瘤生长。在这种情况下，TNF 增加了 p-p38 磷酸化和化疗敏感性，同时进一步增强了 IL-8 的产生。
我们的数据表明 ATF2 在 HNSCC 的 TNF 相关机制中起调节作用。其干扰和核激活与生存和细胞因子产生的显著影响相关。
