Details

Autor(en) / Beteiligte

• Chen, Danian
• Livne-bar, Izhar
• Vanderluit, Jackie L
• Slack, Ruth S
• Agochiya, Mahima
• Bremner, Rod

Titel

Cell-specific effects of RB or RB/p107 loss on retinal development implicate an intrinsically death-resistant cell-of-origin in retinoblastoma

Ist Teil von

• Cancer cell, 2004-06, Vol.5 (6), p.539-551

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• Retinogenesis involves expansion of pluripotent progenitors, specification of postmitotic precursors, and terminal differentiation. Rb or Rb/ p107 loss causes retinoblastoma in humans or mice, respectively. One model suggests that Rb- or Rb/ p107-deficient retinal precursors have infinite proliferative capacity but are death-prone and must acquire an antiapoptotic mutation. Indeed, we show that Rb/ p107 loss does not affect progenitor proliferation or precursor specification, but perturbs cell cycle exit in all seven retinal precursors. However, three precursors survive Rb/p107-loss and stop proliferating following terminal differentiation. Tumors arise from precursors that escape this delayed growth arrest. Thus, retinoblastoma arises from a precursor that has extended, not infinite, proliferative capacity, and is intrinsically death-resistant, not death-prone. We suggest that additional lesions common in retinoblastoma overcome growth arrest, not apoptosis.