Gómez-Román J Javier, Saenz Pilar, Molina Miguel, Cuevas González Jorge, Escuredo Kepa, Santa Cruz Simon, Junquera Corina, Simón Laureano, Martínez Antonio, Gutiérrez Baños J Luis, López-Brea Marta, Esparza Clara, Val-Bernal J Fernando
Departamento Anatomiá Patológica Servicio de Urología, Hospital Universitario Marqués de Valdecilla, Servicio Cántabro de Salud, Facultad de Medicina, Universidad de Cantabria, Avenida de Valdecilla s/n, E39008 Santander, Cantabria, Spain.
Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):459-65.
Fibroblast growth factor receptor 3 (FGFR3) mutations have been associated with achondroplastic syndromes and urinary bladder carcinomas. Here we describe changes in FGFR3 mRNA and protein expression in transitional carcinomas and determine the effect of monoclonal antibodies against FGFR3 in RT-112 cell line proliferation.
We used microarray tools to evaluate FGFR3 mRNA expression in 22 urinary bladder carcinomas at different stages (noninvasive pTa, lamina propria invasive pT1, and muscular invasive pT2) and 7 nonneoplastic tissue controls. FGFR3 protein expression was evaluated by Western blotting in 15 different carcinomas and 3 nonneoplastic controls. Two hundred thirty-seven urinary bladder and renal pelvis carcinomas and 21 negative controls were tested on tissue microarrays by immunohistochemistry. The effect on cell proliferation in the RT-112 bladder cancer cell line of monoclonal antibodies against FGFR3 was also evaluated.
Overexpression of FGFR3 mRNA was found in pTa and pT1 stage carcinomas (fold change >8) and in pT2 carcinomas (fold change >4). Nonneoplastic urinary bladder samples do not express FGFR3 protein. However, 83% of pTa, 100% of pT1, and 50% of pT2 carcinomas expressed FGFR3 as determined by Western blotting. By immunohistochemistry, FGFR3 was positive in 71.4% of pTa, 72% of pT1, and 49.2% of pT2 cases as well as 61.5% of upper urinary tract carcinomas. Proliferation of the RT-112 cell line was inhibited with monoclonal antibodies against FGFR3.
FGFR3 seems to play an important role in transitional cell carcinoma development. Our results suggest that FGFR3 antagonists could be developed as possible therapeutics for treatment of urinary tract carcinoma.
成纤维细胞生长因子受体3（FGFR3）突变与软骨发育不全综合征及膀胱癌有关。在此，我们描述FGFR3 mRNA和蛋白在移行细胞癌中的表达变化，并确定抗FGFR3单克隆抗体对RT - 112细胞系增殖的影响。
我们使用微阵列工具评估22例不同分期（非侵袭性pTa、固有层侵袭性pT1和肌层侵袭性pT2）膀胱癌及7例非肿瘤组织对照中FGFR3 mRNA的表达。通过蛋白质印迹法评估15例不同癌组织及3例非肿瘤对照中FGFR3蛋白的表达。通过免疫组织化学在组织微阵列上检测237例膀胱癌和肾盂癌及21例阴性对照。还评估了抗FGFR3单克隆抗体对RT - 112膀胱癌细胞系增殖的影响。
在pTa和pT1期癌组织（倍数变化>8）以及pT2期癌组织（倍数变化>4）中发现FGFR3 mRNA过表达。非肿瘤性膀胱样本不表达FGFR3蛋白。然而，通过蛋白质印迹法测定，83%的pTa、100%的pT1和50%的pT2癌组织表达FGFR3。通过免疫组织化学，FGFR3在71.4%的pTa、72%的pT1、49.2%的pT2病例以及61.5%的上尿路癌中呈阳性。抗FGFR3单克隆抗体抑制了RT - 112细胞系的增殖。
FGFR3似乎在移行细胞癌的发生发展中起重要作用。我们的结果表明，FGFR3拮抗剂可能被开发为治疗尿路癌的潜在疗法。
