Naturally death-resistant precursor cells revealed as the origin of retinoblastoma.
The molecular mechanisms and the cell-of-origin leading to retinoblastoma are not well defined. In this issue of Cancer Cell, Bremner and colleagues describe the first inheritable model of retinoblastoma, revealing that loss of the pocket proteins pRb and p107 deregulates cell cycle exit in retinal precursors. The authors show that a subset of these precursors contain an inherent resistance to apoptosis, and that while most terminally differentiate, some are likely to acquire additional mutations, leading to tumor formation. Thus, this work defines the cell-of-origin of retinoblastoma and suggests that mutations giving increased proliferative capacity are required for retinoblastoma development.
Trinh
Emmanuelle
E
European Institute of Oncology, Department of Experimental Oncology, Via Ripamonti 435, 20141 Milan, Italy.
Lazzerini Denchi
Eros
E
Helin
Kristian
K
D000483:Alleles; D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002454:Cell Differentiation; D002455:Cell Division; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000502:physiology
D016160:Retinoblastoma Protein