Journal of Biomedical Science

, Volume 13, Issue 3, pp 357–371 | Cite as

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

  • Shu Huang
  • Qun Shen
  • Wen-Ge Mao
  • Ai-Ping Li
  • Jian Ye
  • Qi-Zhan Liu
  • Chang-Ping Zou
  • Jian-Wei Zhou
Article

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

JWA ATRA HL-60 cells differentiation RNA interference 

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Copyright information

© National Science Council Taipei 2006

Authors and Affiliations

  • Shu Huang
    • 1
  • Qun Shen
    • 1
    • 2
  • Wen-Ge Mao
    • 1
  • Ai-Ping Li
    • 1
  • Jian Ye
    • 1
  • Qi-Zhan Liu
    • 1
  • Chang-Ping Zou
    • 3
  • Jian-Wei Zhou
    • 1
  1. 1.Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratory of Human Functional Genomics and Applied Toxicology, School of Public HealthNanjing Medical UniversityNanjingChina
  2. 2.Department of HematologyThe Traditional Chinese Medicine Hospital of Jiangsu ProvinceNanjingChina
  3. 3.Department of OB/Gyn and Department of UrologyThe University of ArizonaTucsonUSA

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