Journal of Biomedical Science

, Volume 13, Issue 3, pp 357–371

JWA, a novel signaling molecule, involved in all-trans retinoic acid induced differentiation of HL-60 cells

Authors

  • Shu Huang
    • Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratory of Human Functional Genomics and Applied Toxicology, School of Public HealthNanjing Medical University
  • Qun Shen
    • Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratory of Human Functional Genomics and Applied Toxicology, School of Public HealthNanjing Medical University
    • Department of HematologyThe Traditional Chinese Medicine Hospital of Jiangsu Province
  • Wen-Ge Mao
    • Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratory of Human Functional Genomics and Applied Toxicology, School of Public HealthNanjing Medical University
  • Ai-Ping Li
    • Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratory of Human Functional Genomics and Applied Toxicology, School of Public HealthNanjing Medical University
  • Jian Ye
    • Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratory of Human Functional Genomics and Applied Toxicology, School of Public HealthNanjing Medical University
  • Qi-Zhan Liu
    • Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratory of Human Functional Genomics and Applied Toxicology, School of Public HealthNanjing Medical University
  • Chang-Ping Zou
    • Department of OB/Gyn and Department of UrologyThe University of Arizona
    • Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratory of Human Functional Genomics and Applied Toxicology, School of Public HealthNanjing Medical University
Article

DOI: 10.1007/s11373-005-9068-0

Cite this article as:
Huang, S., Shen, Q., Mao, W. et al. J Biomed Sci (2006) 13: 357. doi:10.1007/s11373-005-9068-0

Summary

JWA (AF070523) was originally identified as a novel all-trans retinoic acid (ATRA) responsible gene in primary human tracheal bronchial epithelial cells. For the notable performance achieved by ATRA in the differentiation induction therapy, we investigated the role of JWA in ATRA-mediated differentiation of the human myeloid leukemia HL-60 cells. We found that concomitant with the progressive cell differentiation, JWA expression was up-regulated by ATRA in a dose- and time-dependent manner. Inhibition of JWA expression by RNA interference partially blocked ATRA-induced differentiation and growth inhibition of HL-60 cells. Pre-treatment of phorbol-12-myristate-13-acetate (TPA), a PKC activator, decreased ATRA-mediated differentiation, companied with the down-regulation of JWA expression. Arsenic trioxide (As2O3, 0.5  \(\upmu\)M) enhanced the cellular differentiation induced by 0.01  \(\upmu\)M ATRA, but had no noticeable effect on the differentiation induced by 0.1 \(\upmu\)M ATRA. Concurrent with the enhancement, JWA expression was up-regulated. All the data suggest that up-regulation of JWA expression is essential for ATRA-induced differentiation of HL-60 cells. And JWA, associated with PKC, is involved in its signal pathways. Ideal therapeutic efficacy with low toxicity may be obtained if low doses of ATRA (0.01 \(\upmu\)M) and As2O3 (0.5  \(\upmu \)M) are combined. These findings may present a novel mechanism that cellular differentiation and growth inhibition induced by ATRA are mediated at least in part through regulation of JWA expression. JWA may be a novel molecular marker for ATRA-induced HL-60 cell differentiation. ATRA up-regulates JWA expression by stimulating the transcriptional activity of JWA gene promoter.

Keywords

JWAATRAHL-60 cellsdifferentiationRNA interference
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© National Science Council Taipei 2006