Nakashima Dai, Uzawa Katsuhiro, Kasamatsu Atsushi, Koike Hirofumi, Endo Yosuke, Saito Kengo, Hashitani Susumu, Numata Tsutomu, Urade Masahiro, Tanzawa Hideki
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Int J Cancer. 2006 Feb 1;118(3):704-13. doi: 10.1002/ijc.21318.
Adenoid cystic carcinoma (ACC) is one of the most common malignant tumors of the salivary glands. It tends to grow slowly but is associated with a poor prognosis compared to other malignant salivary gland tumors. To identify specific markers of ACC, we examined protein expression profiling in ACC xenograft and normal salivary glands (NSG) using fluorescent 2-dimensional differential in-gel electrophoresis (2-D-DIGE), an emerging technique for comparative proteomics, that improves the reproducibility and reliability of differential protein expression analysis between the samples. To identify the proteins, matrix-assisted laser desorption/ionization time-of-flight peptide mass fingerprinting was carried out. Using these strategies, we detected 4 upregulated proteins and 5 downregulated proteins in ACC xenograft. Maspin and stathmin were selected for further analyses. Western blotting and immunohistochemical staining showed a higher expression of these proteins in ACC xenograft and clinical ACC tissue compared to NSG. Furthermore, Expression of these proteins was correlated with the histologic grading of ACC (n = 10). Therefore, our data indicate that maspin and stathmin may be not only useful biomarkers of ACC but also markers of biologic behavior in this tumor.
腺样囊性癌（ACC）是涎腺最常见的恶性肿瘤之一。它往往生长缓慢，但与其他涎腺恶性肿瘤相比，预后较差。为了鉴定ACC的特异性标志物，我们使用荧光二维差异凝胶电泳（2-D-DIGE）检测了ACC异种移植瘤和正常涎腺（NSG）中的蛋白质表达谱，这是一种用于比较蛋白质组学的新兴技术，可提高样品间差异蛋白质表达分析的重现性和可靠性。为了鉴定这些蛋白质，进行了基质辅助激光解吸/电离飞行时间肽质量指纹分析。使用这些策略，我们在ACC异种移植瘤中检测到4种上调蛋白和5种下调蛋白。选择组织蛋白酶抑制剂和微管相关蛋白进行进一步分析。蛋白质印迹和免疫组织化学染色显示，与NSG相比，这些蛋白在ACC异种移植瘤和临床ACC组织中的表达更高。此外，这些蛋白的表达与ACC的组织学分级相关（n = 10）。因此，我们的数据表明，组织蛋白酶抑制剂和微管相关蛋白不仅可能是ACC的有用生物标志物，而且也是该肿瘤生物学行为的标志物。
