Michor Franziska, Iwasa Yoh, Komarova Natalia L, Nowak Martin A
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
Curr Biol. 2003 Apr 1;13(7):581-4. doi: 10.1016/s0960-9822(03)00172-6.
Tissues of long-lived multicellular organisms have to maintain a constant number of functioning cells for many years. This process is called homeostasis. Homeostasis breaks down when cells emerge with mutations in tumor suppressor genes or oncogenes. Such mutated cells can have increased net rates of proliferation, which is increased somatic fitness. We show that the best protection against such mutations is achieved when homeostasis is regulated locally via small compartments. Small compartments, on the other hand, allow the accumulation of cells with reduced somatic fitness. Cells with mutations conferring genetic instability normally have a reduced somatic fitness because they have an increased probability of producing deleterious mutations or triggering apoptosis. Thus, small compartments protect against mutations in tumor suppressor genes or oncogenes but promote the emergence of genetic instability.
长寿多细胞生物的组织必须在许多年里维持功能细胞数量的恒定。这个过程被称为稳态。当细胞出现肿瘤抑制基因或癌基因突变时，稳态就会被打破。这种突变细胞的净增殖率可能会增加，这就是体细胞适应性的提高。我们表明，当通过小隔室在局部调节稳态时，能实现对这种突变的最佳保护。另一方面，小隔室会使体细胞适应性降低的细胞积累。具有导致基因不稳定突变的细胞通常体细胞适应性降低，因为它们产生有害突变或引发细胞凋亡的概率增加。因此，小隔室可防止肿瘤抑制基因或癌基因突变，但会促进基因不稳定的出现。
