Kan Takatsugu, Yamasaki Seiji, Kondo Kan, Teratani Naoki, Kawabe Atsushi, Kaganoi Junichi, Meltzer Stephen J, Imamura Masayuki, Shimada Yutaka
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Sakyo-ku, Japan.
Oncology. 2006;70(1):25-33. doi: 10.1159/000091183. Epub 2006 Jan 27.
To detect new specific gene expressions in squamous cell carcinoma of the esophagus.
Representational difference analysis of cDNA (cDNA RDA) was applied to a human esophageal cancer cell line (KYSE170) and a human esophageal epithelial cell line (HEEC-1).
LAGE-1 was expressed specifically in KYSE170, but not in HEEC-1. It is also expressed in 27% of esophageal cancer cell lines (3/11) and 33% of esophageal cancer tissues (10/30), but not in other HEECs, normal esophageal epithelium, or other normal tissues except testis, ovary and kidney. The expression of LAGE-1 is strongly correlated with that of MAGE-A1 (p = 0.013, Fisher's exact probability test). Fibronectin, cytokeratin 6B, cytokeratin 19, cyclin D2 and Ten-m2 were detected as candidates for downregulated genes. Reduced expression profiles of them were also identified using cDNA microarrays. The expression of LAGE-1 was induced by 5'-aza-2'-deoxycytidine (5Aza-dC) and trichostatin A (TSA) in esophageal cancer cell lines, which did not express LAGE-1. In HEECs, 5Aza-dC induced LAGE-1 expression, but TSA did not.
LAGE-1 expression was detected in esophageal cancer by cDNA RDA. LAGE-1 might have the potential to be a target antigen for anti-tumoral immunotherapy in esophageal cancers because of its tumor-specific expression similar to that of MAGE-A1.
检测食管鳞状细胞癌中新的特异性基因表达。
将cDNA代表性差异分析(cDNA RDA)应用于一种人食管癌细胞系(KYSE170)和一种人食管上皮细胞系(HEEC-1)。
LAGE-1在KYSE170中特异性表达,而在HEEC-1中不表达。它也在27%的食管癌细胞系(3/11)和33%的食管癌组织(10/30)中表达,但在其他HEEC、正常食管上皮或除睾丸、卵巢和肾脏外的其他正常组织中不表达。LAGE-1的表达与MAGE-A1的表达密切相关(p = 0.013,Fisher精确概率检验)。纤连蛋白、细胞角蛋白6B、细胞角蛋白19、细胞周期蛋白D2和Ten-m2被检测为下调基因的候选基因。使用cDNA微阵列也鉴定出了它们的表达下调情况。在不表达LAGE-1的食管癌细胞系中,5'-氮杂-2'-脱氧胞苷(5Aza-dC)和曲古抑菌素A(TSA)可诱导LAGE-1表达。在HEEC中,5Aza-dC可诱导LAGE-1表达,但TSA不能。
通过cDNA RDA在食管癌中检测到LAGE-1表达。由于LAGE-1与MAGE-A1类似具有肿瘤特异性表达,它可能有潜力成为食管癌抗瘤免疫治疗的靶抗原。