The retinoblastoma gene: its role in cell cycle and cancer

The retinoblastoma gene is the prototype of the tumor suppressor genes, which play critical roles in the genesis of cancer in humans. Although the precise function of the retinoblastoma gene product remains unknown, recent data suggest that it plays dual roles in gating cell cycle progression and promoting cellular differentiation. The molecular mechanisms involved in these roles are becoming clear in some biological systems: pRb binds and sequester several transcription factors to regulate entry of cell cycle and to initiate terminal cellular differentiation. However, it is difficult to rationalize the expression of pRb in a wide range of tissues with the fact that only limited cell types are susceptible to tumor formation when Rb expression is lost. Recent characterizations of Rb-associated proteins may provide some clues as to how Rb function may be differentially modulated in a cell type-specific manner.