REGULATION OF HEMATOPOIETIC CELLS VIA TUMOR SUPPRESSOR GENE WT1

Wilms肿瘤抑制基因WT1的产物被认为是调节细胞生长和分化的组织特异性转录因子。在几种造血、肾和胚胎细胞的细胞分化过程中，WT1表达下调。考虑到这些数据，下调WT1表达可能导致细胞分化。因此，阐明WT1表达的调控机制似乎对控制细胞分化至关重要。在本项目中，我们研究了WT1 mRNA表达的调控机制，并试图控制WT1的表达水平。结果表明，几种WT1基因转染物均未出现明显的生物学效应。我们发现G-CSF上调了人红细胞白血病K562细胞中WT1 mRNA的表达水平。然而，G-CSF既不能诱导细胞增殖，也不能诱导细胞分化。因此，我们认为WT1的表达水平与细胞分化没有直接关系。为了澄清这一建议，我们正在调查我们发现的观察结果是否适用于其他细胞类型。

The product of the Wilms tumor suppressor gene, WT1, is thought to be a tissue specific transcriptional factor regulating cell growth and differentiation. During cellular differentiation of several hematopoietic, renal and embryonal cells, WT1 expression is downregulated.Considering these data, downregulation of WT1 expression may lead to cellular differentiation. Thus, clarification of regulation of WT1 expression seems to be crucial to control cell differentiation, In this project, we have investigated machinery of regulation of WT1 mRNA expression and tried control WT1 expression levels. The results showed no significant biological effects appeared in several WT1 gene transfectants. We found that G-CSF upregulates the levels of WT1 mRNA expression in human erythroid leukemia K562 cells.However, G-CSF induced neither cellular proliferation nor differentiation of the cells. Thus, we propose that levels of WT1 expression is not directly correlated with cellular differentiation. In order to clarify this proposal, we are investigating whether the observations we found are applied to other cell types.