Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer

被引：100
作者：
Morikawa, Teppei [1 ]
Maeda, Daichi
Kume, Haruki [2 ]
Homma, Yukio [2 ]
Fukayama, Masashi
机构：
[1] Univ Tokyo, Dept Pathol, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan
[2] Univ Tokyo, Dept Urol, Grad Sch Med, Tokyo 1130033, Japan
来源：
HISTOPATHOLOGY | 2010年 / 57卷 / 06期
关键词：
bladder cancer; gemcitabine; immunohistochemistry; ribonucleotide reductase M2 subunit; urothelial carcinoma; MESSENGER-RNA EXPRESSION; IDENTIFICATION; GEMCITABINE; TRIAL; P53;
D O I：
10.1111/j.1365-2559.2010.03725.x
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer Aims: To examine the immunohistochemical expression and function of ribonucleotide reductase M2 subunit (RRM2), a gemcitabine-related molecule, in bladder cancer. Methods and results: One hundred and seventeen bladder specimens on a tissue microarray were immunostained for RRM2. Positive RRM2 staining was observed in none of 14 examples of non-neoplastic urothelium, none of four low-grade urothelial carcinoma (UC), 69 of 83 (83%) high-grade UC, three of three (100%) squamous cell carcinoma and 12 of 13 (92%) lymph node metastasis of UC. RRM2 overexpression was associated significantly with muscularis propria invasion in UC patients who had undergone radical cystectomy (P = 0.005). Immunohistochemistry for RRM2 was then applied to small biopsy specimens of 15 cystitis with reactive atypia cases and 25 urothelial carcinoma in-situ (CIS) cases. Positive RRM2 staining was found in one of 15 (6.7%) cystitis with reactive atypia cases and in 24 of 25 (96%) CIS cases. Finally, UM-UC-3 bladder cancer cells were transfected with RRM2 siRNAs and cell growth was evaluated. Knockdown of RRM2 protein markedly inhibited cell growth. Conclusions: We have shown frequent overexpression of RRM2 protein and its possible role in bladder cancer. Our results suggest that RRM2 is a novel diagnostic marker and a potential therapeutic target in bladder cancer.
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页码：885 / 892
页数：8
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