Pre-B-cell leukemia transcription factor 1 is a major target of promyelocytic leukemia zinc-finger-mediated melanoma cell growth suppression
Pre-B-cell leukemia transcription factor 1 is a major target of promyelocytic leukemia zinc-finger-mediated melanoma cell growth suppression
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DOI：
10.1038/sj.onc.1209800
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发表时间：
2007-01-01
期刊：
影响因子：
8
通讯作者：
Higashiyama, S.
中科院分区：
文献类型：
--
作者：
Shiraishi, K.;Yamasaki, K.;Higashiyama, S.
早幼粒细胞白血病锌指（PLZF）是一种转录抑制因子和肿瘤抑制因子。PLZF在黑素细胞中表达，但在黑素瘤细胞中不表达，PLZF表达的恢复显著抑制黑素瘤细胞生长。PLZF调控的几个靶基因已被鉴定，但PLZF的确切功能仍不确定。在此，我们通过DNA微阵列分析寻找PLZF的候选靶基因。前B细胞白血病转录因子1（Pbx 1）是其中一个显著受抑制的基因。Pbx 1在黑色素瘤细胞中高度表达，并且其表达通过用PLZF基因转导而降低。此外，PLZF介导的生长抑制通过Pbx 1的强制表达而逆转。通过特异性小干扰RNA敲低Pbx 1抑制黑色素瘤细胞生长。我们还发现Pbx 1结合HoxB 7。逆转录-聚合酶链反应分析表明，抑制Pbx 1 PLZF降低HoxB 7靶基因的表达，包括肿瘤相关的新血管生成因子，如碱性成纤维细胞生长因子，血管生成素-2和基质金属蛋白酶9。这些发现表明，由于PLZF表达的丧失导致的Pbx 1表达的失调有助于黑色素瘤的进展和/或发病机制。
Promyelocytic leukemia zinc-finger ( PLZF) is a transcriptional repressor and tumor suppressor. PLZF is expressed in melanocytes but not in melanoma cells, and recovery of PLZF expression markedly suppresses melanoma cell growth. Several target genes regulated by PLZF have been identified, but the precise function of PLZF remains uncertain. Here, we searched for candidate target genes of PLZF by DNA microarray analysis. Pre-B-cell leukemia transcription factor 1 (Pbx1) was one of the prominently suppressed genes. Pbx1 was highly expressed in melanoma cells, and its expression was reduced by transduction with the PLZF gene. Moreover, the growth suppression mediated by PLZF was reversed by enforced expression of Pbx1. Knockdown of Pbx1 by specific small interfering RNAs suppressed melanoma cell growth. We also found that Pbx1 binds HoxB7. Reverse transcription-polymerase chain reaction analysis demonstrated that repression of Pbx1 by PLZF reduces the expression of HoxB7 target genes, including tumor-associated neoangiogenesis factors such as basic fibroblast growth factor, angiopoietin-2 and matrix metalloprotease 9. These findings suggest that deregulation of Pbx1 expression owing to loss of PLZF expression contributes to the progression and/or pathogenesis of melanoma.