标题: Loss of Rb launches cell cycle [打印本页] 作者: 杨柳 时间: 2009-3-6 00:44 标题: Loss of Rb launches cell cycle
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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. / v) v7 h8 D) c; {& s; N* H! ]8 o5 {* g4 l+ _- Z& A
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. - e& N3 Q6 Q8 c) n5 F* b( U6 V8 v v# D5 _5 G. K/ S
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 team deleteted Rb in embryonic fibroblasts derived from these mice, they began to see effects. Quiescent fibroblasts exposed to Cre recombinase entered the cell cycle despite the fact that p107 was present. Senescent cells reacted in a similar manner. . z1 S% ]0 F9 l$ q0 g: S: T3 l) N Z. o) s* k$ w# u7 \
In both cases, p107 expression increased after several days, indicating that there is a window for cell proliferation after the loss of Rb. Says Jacks, "even if in vivo this is a transient effect, we still have uncovered a situation where loss of Rb function alone could expand a population in which further cancer-associated mutation might occur."3 B. m/ B8 v1 i E2 f7 P
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Reference: 9 M* g" X. \2 u5 q6 W/ C8 \6 L1 q % z4 r: |, ? r0 YSage, J. 2003. Nature. 424:223–228.(Rapid loss of Rb (right; open bars) in f)作者: txxxtyq 时间: 2015-5-24 18:17