Walker C, Rutten F, Yuan X, Pass H, Mew D M, Everitt J
Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Smithville 78957.
Cancer Res. 1994 Jun 15;54(12):3101-6.
Induction of mesothelioma in the rat is an important animal model for assessing the carcinogenic potential of fibers and for understanding the molecular basis underlying the development of these tumors. Mesotheliomas and nephroblastoma (Wilms' tumor) have many developmental, biochemical, and histological similarities; however, the expression of the Wilms' tumor suppressor gene, WT-1, has not been well characterized in the rat, and its expression pattern in rat or human mesothelioma has not been described. We report that WT-1 transcripts (3.2 kilobases) could be detected by Northern analysis in adult rat testis, spleen, kidney, lung, heart, and glomerular mesangial cells. Normal adult mesothelial cells also expressed this gene. Rat mesothelioma cell lines expressed WT-1 transcripts of 3.2 kilobases and an additional 2.8-kilobase transcript, previously only reported to be expressed in the testis. Normal and transformed rat mesothelial cells expressed all four of the WT-1 splice variants, except testis, which only expressed WT-1 splice variants containing exon 5. Seven of seven human mesothelioma cell lines examined also expressed WT-1 transcripts, suggesting that expression of this gene may be useful in the diagnosis of these tumors.
在大鼠中诱发间皮瘤是评估纤维致癌潜力以及理解这些肿瘤发生发展分子基础的重要动物模型。间皮瘤和肾母细胞瘤（威尔姆斯瘤）在发育、生化及组织学方面有许多相似之处；然而，威尔姆斯瘤抑制基因WT-1在大鼠中的表达尚未得到充分表征，其在大鼠或人类间皮瘤中的表达模式也未见报道。我们报告，通过Northern分析可在成年大鼠睾丸、脾脏、肾脏、肺、心脏及肾小球系膜细胞中检测到WT-1转录本（3.2千碱基）。正常成年间皮细胞也表达该基因。大鼠间皮瘤细胞系表达3.2千碱基的WT-1转录本以及另外一个2.8千碱基的转录本，此前仅报道其在睾丸中表达。正常及转化的大鼠间皮细胞表达所有四种WT-1剪接变体，睾丸除外，睾丸仅表达含外显子5的WT-1剪接变体。所检测的七个人类间皮瘤细胞系中有七个也表达WT-1转录本，提示该基因的表达可能有助于这些肿瘤的诊断。
