Viel A, Giannini F, Capozzi E, Canzonieri V, Scarabelli C, Gloghini A, Boiocchi M
Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano (PN), Italy.
Int J Cancer. 1994 May 15;57(4):515-21. doi: 10.1002/ijc.2910570413.
The frequent allelic deletions observed on the short arm of chromosome 11 in ovarian tumors suggest that the WT1 gene, a proposed tumor-suppressor gene located on chromosome 11p13 and expressed in the human fetal genitourinary system, may contribute to the development of ovarian neoplasms. Structural and sequence analysis of the entire coding portions of the WT1 gene did not reveal any abnormalities in the 20 ovarian tumor specimens (13 of which showed 11p13 allelic deletions) and 5 cell lines which we analyzed. These findings invalidate the hypothesis that the WT1 gene functions as a classical tumor-suppressor gene in ovarian tumorigenesis and suggest that a different recessive oncogene may be "exposed" by the observed 11p13 allelic deletions. Expression analysis showed that the WT1 gene was transcriptionally active in all the tumors tested, but considerable variations in the mRNA levels were found. This apparent variability, which should be confirmed at the cellular level in the tumor specimens, was also observed in the ovarian tumor-cell lines. Finally, WT1 expression data were evaluated in conjunction with immunohistochemical data on p53. The possible functional effects of altered WT1 mRNA expression in ovarian tumors are discussed, taking into account the potential WT1/p53 protein interaction.
在卵巢肿瘤中观察到的11号染色体短臂上频繁的等位基因缺失表明，WT1基因（一个位于11号染色体p13且在人类胎儿泌尿生殖系统中表达的假定肿瘤抑制基因）可能参与了卵巢肿瘤的发生发展。对WT1基因整个编码区的结构和序列分析显示，在我们分析的20个卵巢肿瘤标本（其中13个显示11p13等位基因缺失）和5个细胞系中未发现任何异常。这些发现否定了WT1基因在卵巢肿瘤发生过程中作为经典肿瘤抑制基因发挥作用的假说，并提示一个不同的隐性癌基因可能因观察到的11p13等位基因缺失而“暴露”。表达分析表明，WT1基因在所有检测的肿瘤中均具有转录活性，但mRNA水平存在显著差异。这种明显的变异性（应在肿瘤标本的细胞水平上予以证实）在卵巢肿瘤细胞系中也有观察到。最后，结合p53的免疫组化数据对WT1表达数据进行了评估。考虑到潜在的WT1/p53蛋白相互作用，讨论了卵巢肿瘤中WT1 mRNA表达改变可能产生的功能影响。
