Differential expression of Wnt13 isoforms during leukemic cell differentiation.

Differential expression of Wnt13 isoforms during leukemic cell differentiation.
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DOI：
10.3892/or.20.1.195
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发表时间：
2008-07
期刊：
Oncology reports
影响因子：
4.2
通讯作者：
R. Bunaciu;T. Tang;Catherine D. Mao
R. Bunaciu;T. Tang;Catherine D. Mao
中科院分区：
医学3区
文献类型：
--
作者：
R. Bunaciu;T. Tang;Catherine D. Mao

文献摘要

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Wnt 蛋白控制发育过程中的细胞命运和分化。 Wnt/β-连环蛋白信号通路的改变和 wnt 基因表达的变化显然与白血病相关。人 wnt13/wnt2b 的表达很复杂，因为它涉及替代启动子和 RNA 剪接，产生 Wnt13A、-B 和 -C mRNA 亚型，这些亚型编码具有不同细胞内定位和功能的蛋白质。我们研究了人类 wnt13 的表达与白血病细胞分化的关系。在各种内皮细胞和白血病细胞系中，分化的内皮细胞表达最高水平的 Wnt13 mRNA 亚型。 U937细胞向单核细胞/巨噬细胞的分化导致Wnt13B和-C mRNA增加，而Wnt13A mRNA减少。 K562细胞向巨核细胞的分化伴随着所有Wnt13 mRNA亚型的上调。在两个分化系统中，Wnt13B和-C表达与MAF-B转录因子的表达相关。我们的数据证明了 Wnt13 启动子的差异调节，并在白血病 U937 细胞向单核细胞/巨噬细胞谱系分化过程中精确定位了 Wnt13 亚型转换，从而表明了该过程中的新参与者。
Wnt proteins control cell fate and differentiation during development. Alterations of the Wnt/beta-catenin signaling pathway and changes in wnt gene expression are clearly associated with leukemia. The expression of human wnt13/wnt2b is complex as it involves alternative promoters and RNA splicing giving rise to Wnt13A, -B and -C mRNA isoforms, which encode proteins with different intracellular localizations and functions. We investigated the expression of the human wnt13 in relation to leukemic cell differentiation. Differentiated endothelial cells expressed the highest levels of Wnt13 mRNA isoforms among various endothelial and leukemic cell lines. The differentiation of U937 cells towards monocyte/macrophages resulted in an increase of Wnt13B and -C mRNAs while Wnt13A mRNAs were decreased. The differentiation of K562 cells towards megakaryocytes was accompanied with the up-regulation of all Wnt13 mRNA isoforms. In the two differentiation systems, Wnt13B and -C expression correlated with the expression of the MAF-B transcription factor. Our data demonstrate the differential regulation of wnt13 promoters and pinpoint a Wnt13 isoform switch during differentiation of the leukemic U937 cells towards the monocyte/macrophage lineage, thereby suggesting new players in this process.