ERAP140/Nbla10993 is a novel favorable prognostic indicator for neuroblastoma induced in response to retinoic acid

Hiroshi Arai, Toshinori Ozaki, Hidetaka Niizuma, Yohko Nakamura, Miki Ohira, Kunio Takano, Masahiko Matsumoto, Akira Nakagawara

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

In the present study, we identified a gene termed Nbla10993 whose expression levels are higher in favorable neuroblastomas versus unfavorable ones. Structural analysis showed that Nb1a10993 is a novel splicing variant of the ER-associated protein of 140 kDa (ERAP140), which lacks the central acidic as well as the COOH-terminal Cys/His-rich domain. Similarly, ERAP140 was preferentially expressed in favorable neuroblastomas relative to unfavorable ones. During the all-trans-retinoic acid (ATRA)-mediated neuronal differentiation in neuroblastoma-derived RTBM1 cells, the expression levels of ERAP140/ Nbla10993 increased at the mRNA level. Consistent with these observations, the luciferase reporter analysis demonstrated that the ERAP140/ Nbla10993 promoter responds to ATRA. In addition, the immunoprecipitation/immunoblotting experiments showed that ERAP140 forms a stable complex with RARα but not with RXRα in cells, suggesting that ERAP140 is involved in RAR-mediated transcriptional regulation. Furthermore, the quantitative real-time PCR analysis using 109 primary neuroblastoma samples demonstrated that the expression levels of ERAP140/ Nbla10993 significantly correlate with a better clinical outcome of neuroblastomas. Taken together, our present findings indicate that ERAP140/Nbla10993 plays an important role in the regulation of ATRA-mediated neuronal differentiation, and is a novel member of prognostic indicators for neuroblastoma.

Original languageEnglish
Pages (from-to)1381-1388
Number of pages8
JournalOncology reports
Volume19
Issue number6
Publication statusPublished - 2008 Jun 1
Externally publishedYes

Keywords

  • All-trans-retinoic acid
  • Differentiation
  • ER-associated protein of 140 kDA
  • Nbla10993
  • Neuroblastoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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