Growth-factor-inducible gene expression in senescent human fibroblasts.
Human diploid fibroblasts undergo only a finite number of population doublings in culture. At the end of their life span in culture, human fibroblasts enter an irreversible quiescent state, a process termed cellular senescence. Senescent cells fail to proliferate despite an adequate supply of growth factors in the medium and no apparent change in the number or binding properties of cellular growth factor receptors. In proliferating fibroblast cultures, growth factors have been shown to induce the expression of several genes (growth-related genes). In this report, we review some of our findings on the expression of growth-related genes in senescent cells. We find that the mRNAs for some growth-related genes are not induced by growth factors in senescent cells. By contrast, the mRNAs for other such genes actually increase after human fibroblasts have undergone senescence, although these mRNAs are not necessarily translated efficiently. Our results indicate that multiple changes in gene expression occur during cellular senescence and suggest that the failure to proliferate is a consequence of a more complex change in cellular phenotype, akin to the cessation of proliferation that accompanies terminal differentiation.
Seshadri
T
T
Department of Biochemistry, Boston University Medical School, Massachusetts 02118.
Campisi
J
J
D002470:Cell Survival / Q000502:physiology; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000502:physiology*; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D014176:Protein Biosynthesis; D012333:RNA, Messenger
D006133:Growth Substances; D012333:RNA, Messenger