Down-regulation of Notch-1 expression decreases PU.1-mediated myeloid differentiation signaling in acute myeloid leukemia

Po Min Chen, Chueh Chuan Yen, Wei Shu Wang, Yu Jen Lin, Chiau Jun Chu, Tzeon Jye Chiou, Jin Hwang Liu, Muh Hwa Yang

研究成果: 雜誌貢獻文章同行評審

25 引文 斯高帕斯(Scopus)

摘要

The Notch receptor-mediated signaling pathways control cell fate in many types of organisms including neurogenesis, myogenesis and hematopoiesis in mammalian species. During normal hematopoiesis, Notch-1 promotes myeloid differentiation through up-regulation of the transcriptional factor PU.1. We therefore speculated that down-regulation of Notch-1 expression might be involved in the leukemogenesis of acute myeloid leukemia (AML). Here we investigated Notch-1 expression and its association with PU.1-mediated differentiation signaling in AML. The transcriptional level of Notch-1 and PU.1 was evaluated in 6 AML cell lines and 54 AML patient samples using real-time PCR analysis, and Western blot analysis of Notch-1, PU.1 and one of its downstream targets, the M-CSF receptor (MCSFR), was performed to test for confirmation. A significant decrease in the transcription levels of Notch-1 was noted in AML cell lines and patient samples, and decreased Notch-1 protein expression in AML was confirmed by Western blotting. Down-regulation of Notch-1 expression was associated with a decrease in PU.1/MCSFR expression in AML. Co-immunoprecipitation experiments showed that partial disruption of the Notch-1/PU.1 complex was noted in AML cells. No detectable mutation of Notch-1 (ANK, PEST) and PU.1 (PEST, DBD) was noted by PCR-single-strand conformation polymorphism (SSCP) assay. These results suggest that down-regulation of Notch-1 expression decreases PU.1/MCSFR expression and disrupts the Notch-1/PU.1 complex, which may impede the PU.l-mediated myeloid signaling and contribute to the leukemogenesis of AML.

原文英語
頁(從 - 到)1335-1341
頁數7
期刊International Journal of Oncology
32
發行號6
DOIs
出版狀態已發佈 - 6月 2008
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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