Menke A L, Shvarts A, Riteco N, van Ham R C, van der Eb A J, Jochemsen A G
Laboratory of Molecular Carcinogenesis, Leiden University, the Netherlands.
Cancer Res. 1997 Apr 1;57(7):1353-63.
The Wilms' tumor 1 gene (WT1) encodes a transcription factor of the zinc-finger family. As a result of alternative RNA splicing, the gene can be expressed as four polypeptides that differ in the presence or absence of a stretch of 17 amino acids just NH2 terminal of the four zinc fingers and a stretch of three amino acids (+/-KTS) between zinc fingers 3 and 4. In this study, cDNA constructs encoding the four human Wilms' tumor 1 splice variants were transiently transfected into the p53-negative Hep3B and the p53-positive HepG2 hepatoma cell lines. Morphological assessment of the WT1-expressing cells showed that the WT1(-KTS) splice variants induced apoptosis in both cell lines, whereas the WT1(+KTS) isoforms did not. The induction of apoptosis by the WT1(-KTS) isoforms appears to be p53 independent in the hepatoma cell lines. Furthermore, it was found that the WT1(-KTS)-induced apoptosis could not be suppressed by coexpression of either the Mr 21,000 E1B, the Bcl-2, or the BAG-1 protein. Coexpression of either the epidermal growth factor receptor or the insulin receptor, however, partially rescued the cells from apoptosis.
肾母细胞瘤1基因（WT1）编码一种锌指家族的转录因子。由于RNA可变剪接，该基因可表达为四种多肽，它们在四个锌指的NH2末端是否存在一段17个氨基酸以及锌指3和4之间是否存在一段三个氨基酸（+/-KTS）方面存在差异。在本研究中，将编码四种人肾母细胞瘤1剪接变体的cDNA构建体瞬时转染到p53阴性的Hep3B和p53阳性的HepG2肝癌细胞系中。对表达WT1的细胞进行形态学评估表明，WT1（-KTS）剪接变体在两种细胞系中均诱导细胞凋亡，而WT1（+KTS）同工型则不诱导。WT1（-KTS）同工型诱导的细胞凋亡在肝癌细胞系中似乎与p53无关。此外，发现WT1（-KTS）诱导的细胞凋亡不能被Mr 21,000 E1B、Bcl-2或BAG-1蛋白的共表达所抑制。然而，表皮生长因子受体或胰岛素受体的共表达可部分挽救细胞免于凋亡。
