Wang Nan, Liu Zhi-Hua, Ding Fang, Wang Xiu-Qin, Zhou Chuan-Nong, Wu Min
National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing 100021, China.
World J Gastroenterol. 2002 Dec;8(6):966-70. doi: 10.3748/wjg.v8.i6.966.
Esophageal carcinoma is one of the most common malignant tumors in China. But the molecular mechanisms of esophageal carcinoma remains unclear. Gut-enriched Kruppel-like factor (GKLF) is a newly identified transcription factor which is expressed abandantly in the epithelial cells of the gastrointestinal tract and deregulation of GKLF was linked to several types of cancer. It is of interest to study the expression and role of GKLF in esophageal carcinoma.
Semi-quantitative RT-PCR was used to compare GKLF expression in esophageal squamous cell carcinoma to normal mucosa of the same patients. The serum deprivation inducibility of GKLF was observed in an esophageal squamous cancer cell line by comparison to the primary culture of human fibroblast. The effect of antisense GKLF transfection on the proliferation and adhesion of esophageal squamous cancer cell line was also observed.
The level of GKLF transcript is lower in esophageal squamous cell carcinoma compared to paired normal-appearing mucosa in 14 of 17 of the tumors analyzed. The serum deprivation inducibility of GKLF was greatly decreased in an esophageal squamous cancer cell line compared to the primary culture of human fibroblast. Decreased expression of GKLF in the esophageal cancer cell by antisense GKLF transfection increased its proliferation rate compared with that of vector transfected cell control (P<0.05). Transfection of antisense GKLF decreased its adhesion ability (P<0.05).
The findings of this study demonstrate the down-regulation of GKLF in esophageal squamous cancer, and suggest that deregulation of GKLF may play a role in initiation and/or progression as well as the metastasis of esophageal squamous cancer.
食管癌是中国最常见的恶性肿瘤之一。但其分子机制仍不清楚。肠道富集型Kruppel样因子（GKLF）是一种新发现的转录因子，在胃肠道上皮细胞中大量表达，GKLF失调与多种癌症有关。研究GKLF在食管癌中的表达及作用具有重要意义。
采用半定量逆转录聚合酶链反应（RT-PCR）比较食管癌患者食管鳞状细胞癌与同一患者正常黏膜中GKLF的表达。通过与人类成纤维细胞原代培养比较，观察食管鳞状癌细胞系中GKLF的血清剥夺诱导性。还观察了反义GKLF转染对食管鳞状癌细胞系增殖和黏附的影响。
在分析的17例肿瘤中的14例中，与配对的外观正常黏膜相比，食管鳞状细胞癌中GKLF转录水平较低。与人类成纤维细胞原代培养相比，食管鳞状癌细胞系中GKLF的血清剥夺诱导性大大降低。与载体转染细胞对照相比，反义GKLF转染使食管癌细胞中GKLF表达降低，其增殖率增加（P<0.05）。反义GKLF转染降低了其黏附能力（P<0.05）。
本研究结果表明食管鳞状癌中GKLF表达下调，提示GKLF失调可能在食管鳞状癌的发生和/或进展以及转移中起作用。
