Tsuneoka Makoto, Fujita Hiromasa, Arima Nobuyuki, Teye Kwesi, Okamura Torahiko, Inutsuka Hiroki, Koda Yoshiro, Shirouzu Kazuo, Kimura Hiroshi
Division of Human Genetics, Department of Forensic Medicine, Kurume University School of Medicine, Kurume, Japan.
Clin Cancer Res. 2004 Nov 1;10(21):7347-56. doi: 10.1158/1078-0432.CCR-03-0543.
We previously identified mina53, a novel Myc target gene. Here we investigated whether mina53 is related to esophageal squamous cell carcinoma (ESCC), a disease with poor prognosis.
Mina53 expression was suppressed in ESCC cell lines by a RNA interference method to investigate whether Mina53 is involved in cell proliferation. Expression of Mina53 was investigated by Western blotting in tissue sections from patients with ESCC. Immunohistochemical analysis of Mina53 was carried out and compared with that using anti-Ki-67 antibody. Finally, the level of Mina53 expression was compared with the length of survival of patients with ESCC.
Reduction of mina53 expression by RNA interference suppressed cell proliferation in ESCC cell lines. Western blot analysis of surgically resected ESCC specimens indicated that the expression of Mina53 in tumors was increased compared with that in adjacent nonneoplastic tissues in all four specimens examined. When formalin-fixed specimens from 52 patients with ESCC were stained immunohistochemically, it was found that Mina53 was highly expressed in 83% of specimens. Anti-Mina53 antibody stained tumors more efficiently than antibody against Ki-67, a cell proliferation biomarker, in some cancer specimens. Patients with high expression of Mina53 had shorter survival periods, whereas the expression level of Ki-67 in ESCC showed no relationship to patient outcome.
Taken together, our results indicate that expression of Mina53 is a characteristic feature of ESCC and suggest that immunostaining by anti-Mina53 antibody may be useful as a potential prognostic indicator.
我们之前鉴定出了一种新的Myc靶基因mina53。在此,我们研究了mina53是否与预后较差的食管鳞状细胞癌(ESCC)相关。
通过RNA干扰方法抑制ESCC细胞系中的mina53表达,以研究Mina53是否参与细胞增殖。采用蛋白质免疫印迹法检测ESCC患者组织切片中Mina53的表达。对Mina53进行免疫组化分析,并与使用抗Ki-67抗体的结果进行比较。最后,将Mina53的表达水平与ESCC患者的生存期进行比较。
RNA干扰降低mina53表达可抑制ESCC细胞系的细胞增殖。对手术切除的ESCC标本进行蛋白质免疫印迹分析表明,在所检测的所有4个标本中,肿瘤组织中Mina53的表达均高于相邻的非肿瘤组织。对52例ESCC患者的福尔马林固定标本进行免疫组化染色时发现,83%的标本中Mina53高表达。在一些癌症标本中,抗Mina53抗体比细胞增殖生物标志物抗Ki-67抗体更有效地标记肿瘤。Mina53高表达的患者生存期较短,而ESCC中Ki-67的表达水平与患者预后无关。
综上所述,我们的结果表明Mina53的表达是ESCC的一个特征,并提示抗Mina53抗体免疫染色可能作为一种潜在的预后指标。