Zhang Jian, Gao Fu-Lu, Zhi Hui-Ying, Luo Ai-Ping, Ding Fang, Wu Min, Liu Zhi-Hua
National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
World J Gastroenterol. 2004 Apr 15;10(8):1088-92. doi: 10.3748/wjg.v10.i8.1088.
To investigate the expression patterns of esophageal squamous cell cancer deregulated genes in mid to late stages of C57BL/6J mouse embryogenesis, and the correlation between these genes in embryonic development and tumorigenesis of esophageal squamous cell cancer.
Reverse northern screening was performed to examine the expression patterns of esophageal cancer deregulated genes in C57BL/6J mouse embryogenesis. To confirm the gene expression patterns, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out for 3 of the randomly picked differentially expressed genes.
Within these esophageal cancer deregulated genes, 4 patterns of expression were observed at 3 stages embryonic d 11.5 (E11.5), embryonic d 13.5 (E13.5) and postnatal d1 (P1). (1) Up-regulation during the E11.5 period, down- regulation during the E13.5 and P1 period (up-down-down), the 10 up-regulated genes during the E11.5 period could be classified into 6 known genes and 4 unknown genes. The known genes included differentiation related genes (S100A8), immunity related gene (IGL), translation and transcription regulation genes (RPL15, EEF1A1), cytoskeletal protein (TUBA1), cysteine protease inhibitor (cystatin B). (2) Up-regulation during the E13.5 and P1 period (down-up-up), such as the SPRR2A which was down-regulated at E11.5. (3) Down-regulation during the E11.5 and E13.5 period (down-down-up), such as RHCG and keratin 4. (4) Fluctuating expression, down initially, up at E13.5, and then down again (down-up-down). EMP1 belonged to such a gene, which was highly expressed at E13.5.
The results will be helpful for understanding the function of esophageal squamous cell carcinoma (ESCC) deregulated genes in embryonic development and tumorigenesis. S100A8 and S100A9 may play different roles in early embryonic development. IGL may be an oncofetal protein, and EMP1 relates with neurogenesis at E13.5. The genes identified pertinent to embryonic development may serve as candidate susceptibility genes for inherited esophageal cancer disorders as well as for various heritable disorders of embryonic development.
研究食管鳞状细胞癌失调基因在C57BL/6J小鼠胚胎发育中后期的表达模式,以及这些基因在胚胎发育与食管鳞状细胞癌肿瘤发生之间的相关性。
采用反向Northern杂交筛选技术检测食管癌失调基因在C57BL/6J小鼠胚胎发育过程中的表达模式。为证实基因表达模式,对随机挑选的3个差异表达基因进行半定量逆转录聚合酶链反应(RT-PCR)。
在这些食管癌失调基因中,于胚胎第11.5天(E11.5)、胚胎第13.5天(E13.5)和出生后第1天(P1)这3个阶段观察到4种表达模式。(1)在E11.5期上调,在E13.5期和P1期下调(上-下-下),E11.5期上调的10个基因可分为6个已知基因和4个未知基因。已知基因包括分化相关基因(S100A8)、免疫相关基因(IGL)、翻译和转录调控基因(RPL15、EEF1A1)、细胞骨架蛋白(TUBA1)、半胱氨酸蛋白酶抑制剂(胱抑素B)。(2)在E13.5期和P1期上调(下-上-上),如在E11.5期下调的SPRR2A。(3)在E11.5期和E13.5期下调(下-下-上),如RHCG和角蛋白4。(4)表达波动,最初下调,在E13.5期上调,然后再次下调(下-上-下)。EMP1属于此类基因,在E13.5期高表达。
这些结果将有助于理解食管鳞状细胞癌(ESCC)失调基因在胚胎发育和肿瘤发生中的功能。S100A8和S S100A9可能在早期胚胎发育中发挥不同作用。IGL可能是一种癌胚蛋白,而EMP1在E13.5期与神经发生相关。鉴定出的与胚胎发育相关的基因可能作为遗传性食管癌疾病以及各种胚胎发育遗传性疾病的候选易感基因。