NDRG2 gene expression in B16F10 melanoma cells restrains melanogenesis via inhibition of Mitf expression

Aeyung Kim, Young Yang, Myeong Sok Lee, Young Do Yoo, Hee Gu Lee, Jong Seok Lim

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

NDRG2 (N-myc downstream-regulated gene 2) is a candidate tumor suppressor implicated in control of glioblastoma proliferation and dendritic cell differentiation. The microphthalmia-associated transcription factor (Mitf) plays a crucial role in the melanocyte lineage and in melanoma by controlling survival, differentiation, cell cycle entry and exit, and melanoma metastasis. Identifying upstream regulators of Mitf expression, therefore, remains a key issue. In this study, we aimed to assess whether the candidate tumor suppressor NDRG2 can modulate Mitf expression. Here, we show that NDRG2 acts to prevent cAMP and β-catenin-mediated activation of the Mitf promoter, thereby blocking melanogenesis via the downstream Mitf target genes Tyrosinase, Tyrp1 and Dct. The data suggest that NDRG2 impairs melanogenesis by interfering with both the TCF/β-catenin and cAMP/CREB pathways that are known to stimulate Mitf expression in melanocytes and have major implications for the role of NDRG2 in pigmentation and melanoma progression. Taken together, the results not only identify NDRG2 as a novel regulator of pigmentation, but also potentially a key factor in regulating melanoma progression via Mitf.

Original languageEnglish
Pages (from-to)653-664
Number of pages12
JournalPigment Cell and Melanoma Research
Volume21
Issue number6
DOIs
Publication statusPublished - 2008 Dec

Keywords

  • Melanogenesis
  • Mitf
  • NDRG2
  • TCF/β-catenin
  • cAMP

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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