Expression of tyrosinase-related protein 2/DOPAchrome tautomerase in the retinoblastoma

Tetsuo Udono, Kazuhiro Takahashi, Ken ichi Yasumoto, Miki Yoshizawa, Kazuhisa Takeda, Toshiaki Abe, Makoto Tamai, Shigeki Shibahara

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Tyrosinase-related protein 2 (TRP-2), also known as DOPAchrome tautomerase, is an enzyme in melanin biosynthesis and may play an important role in detoxification of a metabolite derived from DOPA. TRP-2 is expressed in melanocytes of neural crest origin and retinal pigment epithelium (RPE), derived from the optic cup. TRP-2 has been established as an early differentiation marker for melanoblasts and RPE. It is therefore of significance to study the regulation of TRP-2/DOPAchrome tautomerase expression. Here we show that TRP-2 mRNA is expressed in Y79 human retinoblastoma cell line, derived from a primitive multipotential retinal cell. Retinoblastoma is the common primary intraocular tumor of childhood. Basal expression levels in Y79 retinoblastoma cells of TRP-2 mRNA and protein are comparable to those in melanoma cells, whereas mRNA for tyrosinase, the rate-limiting enzyme in melanogenesis, is undetectable in retinoblastoma cells. Transient transfection assays showed that the TRP-2 gene promoter efficiently directs the reporter gene expression in retinoblastoma cells as it does in melanoma cells. Moreover, the expression of TRP-2 mRNA was induced by retinoic acid in retinoblastoma cells but not noticeably affected by forskolin, a cAMP-elevating reagent, whereas in melanoma cells its expression was induced by forskolin but not by retinoic acid. These results suggest a difference in the regulation of TRP-2 expression between retinoblastoma and melanoma cells. Moreover, TRP-2 mRNA is expressed in the excised retinoblastoma specimens, as assessed by RT-PCR. The present study shows unexpected features of TRP-2 and may enhance our understanding of the pathophysiology of retinoblastoma.

Original languageEnglish
Pages (from-to)225-234
Number of pages10
JournalExperimental Eye Research
Volume72
Issue number3
DOIs
Publication statusPublished - 2001

Keywords

  • DOPA
  • DOPAchrome tautomerase
  • Differentiation
  • Melanogenesis
  • Melanoma
  • Neural crest
  • Retinal pigment epithelium
  • Retinoblastoma
  • Tyrosinase-related protein 2

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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