Loss of Id2 potentiates the tumorigenic effect of Rb inactivation in a mouse model of retinoblastoma

Solange Landreville, Duanduan Ma, Jun Wu, J. William Harbour

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Purpose: In some cancers, the oncogenic consequences of inactivating the retinoblastoma protein (Rb) appear to be mediated by unrestrained activity of the inhibitor of DNA binding protein Id2. The role of Id2 has not yet been investigated in the prototype cancer Rb-defective cancer, retinoblastoma itself. This study investigated whether loss of Id2 modified the effects of Rb inactivation in a mouse model of retinoblastoma. Methods: Id2 was analyzed in cultured cells using qPCR, Western blot, and colony formation assays. LHβ-Tag transgenic mice were crossed with Id2 heterozygotes to obtain mice with all three Id2 genotypes. Intraocular tumors were assessed for size, degree of differentiation, mitotic index, and tumor vascular density at 15 weeks of age. Results: Retinoblastoma cell lines expressed low levels of Id2 mRNA and protein. Depletion of Id2 in Rb-inactivated cells increased clonogenic activity. Id2-deficient tumors in vivo were significantly larger, less differentiated, and more vascularized than Id2-wild-type tumors (P=0.02, P=0.01, P=0.0001, respectively). There was a dosage effect for loss of each Id2 allele with respect to differentiation and vascular density. Conclusions: Id2 suppresses rather than promotes tumor progression in this mouse model of retinoblastoma. Id2 can act as either an oncogene or a tumor suppressor depending on context.

Original languageEnglish (US)
Pages (from-to)435-439
Number of pages5
JournalCurrent Eye Research
Volume35
Issue number5
DOIs
StatePublished - May 2010

Keywords

  • Id2
  • Pocket proteins
  • Rb protein
  • Retinoblastoma
  • Tumor suppressor

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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