Laboratory of Biomedical Ultrasonics/Gynecological Oncology Laboratory, West China Second University Hospital, Sichuan University, Chengdu, PR China.
Gynecol Oncol. 2011 Oct;123(1):123-8. doi: 10.1016/j.ygyno.2011.07.003. Epub 2011 Jul 24.
To investigate the correlation of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its specific receptor fibroblast growth factor-inducible immediate-early response protein 14 (Fn14) to cervical carcinogenesis by examining TWEAK/Fn14 expression levels or locations in different cervical tissues and cells.
TWEAK/Fn14 mRNA expressions were detected by quantitative real-time PCR in total of 120 cervical samples including normal, precancerous and cancerous tissues, while protein expressions were detected by immunofluorescent staining and western blot in both tissues and cell lines. Correlation between TWEAK expression levels to cancer progression and clinicopathologic features was statistically analyzed.
The TWEAK expression was significantly decreased while Fn14 expression was increased in carcinoma and cervical intraepithelial neoplasm (CIN) specimens compared with that in normal control specimens. A similar trend of TWEAK/Fn14 expression was also observed in cervical cell lines. In addition, TWEAK expression decreased further along with the interstitial depth of invasion (P<0.05) and tumor grade (P<0.05), suggesting that TWEAK acts rather on local cancer tissue infiltration.
TWEAK/Fn14 pathway may play a role in the development of squamous cervical carcinoma, in which the reduced level of TWEAK could promote the progression and invasion of cervical cancer. An increase in Fn14 may reflect a compensatory response to decreased TWEAK and may provide a novel therapeutic target for human cervical cancer treatment or a biomarker for cervical cancer diagnosis.
通过检测不同宫颈组织和细胞中肿瘤坏死因子样凋亡弱诱导剂（TWEAK）及其特异性受体成纤维细胞生长因子诱导的早期即刻反应蛋白 14（Fn14）的表达水平或位置，探讨 TWEAK/Fn14 与宫颈癌发生的相关性。
采用实时定量 PCR 检测 120 例宫颈组织（包括正常、癌前病变和癌组织）中 TWEAK/Fn14mRNA 的表达，免疫荧光染色和 Western blot 检测组织和细胞系中 TWEAK/Fn14 的蛋白表达。统计分析 TWEAK 表达与癌症进展及临床病理特征的相关性。
与正常对照组相比，癌组织和宫颈上皮内瘤变（CIN）标本中 TWEAK 的表达明显降低，而 Fn14 的表达明显升高。在宫颈细胞系中也观察到类似的 TWEAK/Fn14 表达趋势。此外，TWEAK 表达随着间质浸润深度（P<0.05）和肿瘤分级（P<0.05）的增加而进一步降低，提示 TWEAK 主要作用于局部癌组织浸润。
TWEAK/Fn14 通路可能参与宫颈鳞癌的发生发展，TWEAK 水平的降低可能促进宫颈癌的进展和侵袭。Fn14 的增加可能反映了对 TWEAK 降低的代偿反应，可为宫颈癌的治疗提供新的治疗靶点或宫颈癌诊断的生物标志物。
