Zhang Tao, Zheng Jingcun, Liu Chunfang, Lu Yuan
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, PR China.
Urol Int. 2009;82(4):380-7. doi: 10.1159/000218524. Epub 2009 Jun 8.
Metastatic renal cell carcinoma (RCC) remains the leading cause of mortality in patients with clear cell RCC. While deleted in liver cancer (DLC-1) is known to be closely associated with tumor growth and metastasis in several kinds of human tumors, the function of DLC-1 in clear cell RCC is unclear.
We quantified DLC-1 mRNA expression in paired tumor and non-tumor samples from 62 patients in clear cell RCC using a real-time reverse transcription polymerase chain reaction (RT-PCR), and DLC-1 protein using Western blotting and immunohistochemistry. The association between DLC-1 and matrix metalloproteinase-2 were analyzed.
A high level of DLC-1 mRNA and protein expression in approximately 90% of normal renal specimens, the expression levels of DLC-1 in the primary tumors with synchronous metastases were lower than in those without metastases (p < 0.01). Furthermore, DLC-1 expression inversely correlated with advanced histological grade and stage (p < 0.05). Moreover, it is likely that down-regulated DLC-1 increases matrix invasion abilities of RCC via enhancing matrix metalloproteinase-2 expression.
Together, it seems that reduced DLC-1 is involved in tumor expansion phenomena associated with tumor progression, invasion and distant metastasis of RCC.
转移性肾细胞癌(RCC)仍然是透明细胞RCC患者死亡的主要原因。虽然已知肝癌缺失基因(DLC-1)在几种人类肿瘤中与肿瘤生长和转移密切相关,但DLC-1在透明细胞RCC中的功能尚不清楚。
我们使用实时逆转录聚合酶链反应(RT-PCR)对62例透明细胞RCC患者的配对肿瘤和非肿瘤样本中的DLC-1 mRNA表达进行定量,并使用蛋白质免疫印迹法和免疫组织化学对DLC-1蛋白进行定量。分析了DLC-1与基质金属蛋白酶-2之间的关联。
在大约90%的正常肾标本中DLC-1 mRNA和蛋白表达水平较高,伴有同步转移的原发性肿瘤中DLC-1的表达水平低于无转移的肿瘤(p<0.01)。此外,DLC-1表达与高级组织学分级和分期呈负相关(p<0.05)。此外,DLC-1表达下调可能通过增强基质金属蛋白酶-2的表达来增加RCC的基质侵袭能力。
总之,似乎DLC-1表达降低与RCC肿瘤进展、侵袭和远处转移相关的肿瘤扩展现象有关。