Loss of Rb launches cell cycle

Unlike germline mutations, acute somatic loss of an important tumor suppressor gene is sufficient to push quiescent cells into the cell cycle, according to Julien Sage, Abigail Miller, Tyler Jacks (MIT, Cambridge, MA), and colleagues.

Although retinoblastoma (RB) mutations are relatively common in human cancers, researchers have been puzzled by the observation that other proteins, including p107, are able to compensate partially for Rb's absence in knock-out mice. In human tumors, in contrast, p107 is present and functional, yet Rb mutations are clearly linked to tumor formation.

To determine whether sporadic somatic mutations, which probably occur during cancer development, induce a different response from germline ones, the team engineered a conditional mutant in which Rb could be excised by Cre recombinase. The homozygous transgenic mice were wild type, but when the...