Kakehi Y, Wu W J, Kim W J, Arao S, Fukumoto M, Yoshida O
Department of Urology, Kyoto University, Japan.
Int J Urol. 1995 Nov;2(5):309-15.
We sought to determine how often P-glycoprotein is involved in the drug-resistance of urothelial cancer, and whether MDR1 gene expression is correlated with tumor grade, invasiveness, or metastasis.
Forty-two tumor specimens and two normal bladder mucosal samples obtained from 34 urothelial cancer patients were analyzed. Reverse-transcription and polymerase chain reaction were conducted. MDR1 mRNA levels were determined by measuring the relative ratio of the MDR1 to beta-2-microglobulin (b2 m) mRNA specific PCR products.
The MDR1/b2 m in two normal urothelial samples were 0.044 and 0.045. For untreated primary tumors, levels of MDR1 gene expression in 46% tumor samples were less than that of normal urothelium, while 27% showed expression levels with a MDR1/b2 m ratio more than 0.1. There was no statistical correlation between MDR1 mRNA level and tumor grade, stage, or metastatic status. There was higher MDR1 gene expression in two lymph node metastasis specimens and almost equal expressions in two more. There was no significant difference in the mean MDR1/b2 m ratio between postchemotherapy and untreated tumors. A remarkable elevation of the MDR1 mRNA level (15 times greater than prechemotherapy) was found in one tumor; mRNA levels of the multidrug resistance-associated protein (MRP) gene, glutathione S-transferase pi (GST-pi) gene or DNA topoisomerase II (topo II) gene did not increase.
It is still unclear whether the MDR1 gene expression in urothelial tumor cells is inducible by the current combination chemotherapy regimens. RT-PCR quantitation is useful for determining the expression level of MDR1 gene in urothelial cancer.
我们试图确定P-糖蛋白参与尿路上皮癌耐药的频率，以及MDR1基因表达是否与肿瘤分级、侵袭性或转移相关。
分析了从34例尿路上皮癌患者获取的42个肿瘤标本和2个正常膀胱黏膜样本。进行了逆转录和聚合酶链反应。通过测量MDR1与β-2-微球蛋白（b2m）mRNA特异性PCR产物的相对比值来确定MDR1 mRNA水平。
两个正常尿路上皮样本中的MDR1/b2m分别为0.044和0.045。对于未经治疗的原发性肿瘤，46%的肿瘤样本中MDR1基因表达水平低于正常尿路上皮，而27%的样本显示MDR1/b2m比值大于0.1。MDR1 mRNA水平与肿瘤分级、分期或转移状态之间无统计学相关性。两个淋巴结转移标本中MDR1基因表达较高，另外两个标本中的表达几乎相等。化疗后与未经治疗的肿瘤之间，平均MDR1/b2m比值无显著差异。在一个肿瘤中发现MDR1 mRNA水平显著升高（比化疗前高15倍）；多药耐药相关蛋白（MRP）基因、谷胱甘肽S-转移酶pi（GST-pi）基因或DNA拓扑异构酶II（topo II）基因的mRNA水平未升高。
目前尚不清楚当前的联合化疗方案是否可诱导尿路上皮肿瘤细胞中的MDR1基因表达。RT-PCR定量分析有助于确定尿路上皮癌中MDR1基因的表达水平。
