Differential regulation of cyclin-dependent kinase inhibitors in neuroblastoma cells

Lan Qiao, Pritha Paul, Sora Lee, Jingbo Qiao, Yongsheng Wang, Dai H. Chung

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Gastrin-releasing peptide (GRP) and its receptor (GRP-R) are highly expressed in undifferentiated neuroblastoma, and they play critical roles in oncogenesis. We previously reported that GRP activates the PI3K/AKT signaling pathway to promote DNA synthesis and cell cycle progression in neuroblastoma cells. Conversely, GRP-R silencing induces cell cycle arrest. Here, we speculated that GRP/GRP-R signaling induces neuroblastoma cell proliferation via regulation of cyclin-dependent kinase (CDK) inhibitors. Surprisingly, we found that GRP/GRP-R differentially induced expressions of p21 and p27. Silencing GRP/GRP-R decreased p21, but it increased p27 expressions in neuroblastoma cells. Furthermore, we found that the intracellular localization of p21 and p27 in the nuclear and cytoplasmic compartments, respectively. In addition, we found that GRP/GRP-R silencing increased the expression and accumulation of PTEN in the cytoplasm of neuroblastoma cells where it co-localized with p27, thus suggesting that p27 promotes the function of PTEN as a tumor suppressor by stabilizing PTEN in the cytoplasm. GRP/GRP-R regulation of CDK inhibitors and tumor suppressor PTEN may be critical for tumoriogenesis of neuroblastoma.

Original languageEnglish (US)
Pages (from-to)295-299
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume435
Issue number2
DOIs
StatePublished - May 31 2013
Externally publishedYes

Keywords

  • GRP
  • Neuroblastoma
  • P21
  • P27
  • PTEN

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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