The Wnt signaling pathway has tumor suppressor properties in retinoblastoma

Shoshana Tell, Hyun Yi, Maria Elena Jockovich, Timothy G. Murray, Abigail S. Hackam

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Retinoblastoma is a pediatric retinal tumor caused by mutational inactivation of the tumor suppressor pRb. Additional genetic changes, as yet unidentified, are believed to be required for tumor initiation. Mutations in the Wnt signaling pathway have been implicated in the pathogenesis of many cancers. Multiple Wnt pathway genes are expressed in the retina and the pRb and Wnt pathways interact biochemically, raising the possibility that alterations in the Wnt pathway contribute to retinoblastoma. Our studies showed that Wnt signaling activation significantly decreased the viability of retinoblastoma cell lines by inducing cell cycle arrest, which was associated with upregulated p53. Furthermore, immunolocalization of the Wnt signaling mediator β-catenin in human and mouse retinoblastoma tissue indicated that canonical Wnt signaling is suppressed in tumors in vivo. These studies are consistent with the Wnt pathway acting as a tumor suppressor in retinoblastoma and suggest that loss of Wnt signaling is tumorigenic in the retina.

Original languageEnglish (US)
Pages (from-to)261-269
Number of pages9
JournalBiochemical and biophysical research communications
Volume349
Issue number1
DOIs
StatePublished - Oct 13 2006

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Keywords

  • β-catenin
  • Cell cycle
  • p53
  • pRb
  • RB1
  • Retinoblastoma
  • Wnt

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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