Failure of senescent human fibroblasts to express the insulin-like growth factor-1 gene

A. Ferber, C. D. Chang, C. Sell, A. Ptasznik, V. J. Cristofalo, K. Hubbard, H. L. Ozer, M. Adamo, C. T. Roberts, D. LeRoith, G. Dumenil, R. Baserga

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58 Scopus citations

Abstract

Senescent human diploid fibroblasts express several growth-regulated genes but fail to express others. In this paper we show, by a very sensitive technique (reverse transcriptase-polymerase chain reaction), that senescent cells fail to express insulin-like growth factor-1 (IGF-1) mRNA, which is expressed in moderate amounts by young cells. Human fibroblasts immortalized by transfection with a temperature-sensitive SV40 T antigen gene regain the ability to express IGF-1 mRNA, but only at the permissive temperature of 34 °C. Under these conditions, the immortalized human fibroblasts grow even in 1% serum. At the restrictive temperature of 39 °C, the temperature-sensitive T antigen is nonfunctional, IGF-1 RNA is not detectable, and the cells fail to grow even in 10% serum. The failure to express IGF-1 mRNA in postsenescent cells can be ascribed, at least in part, to a transcriptional mechanism. Despite the correlation among immortalization by SV40 T antigen, expression of IGF-1, and growth, it seems unlikely that the failure to express IGF-1 is the sole cause of cellular senescence; other requirements must be postulated.

Original languageEnglish (US)
Pages (from-to)17883-17888
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number24
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ferber, A., Chang, C. D., Sell, C., Ptasznik, A., Cristofalo, V. J., Hubbard, K., Ozer, H. L., Adamo, M., Roberts, C. T., LeRoith, D., Dumenil, G., & Baserga, R. (1993). Failure of senescent human fibroblasts to express the insulin-like growth factor-1 gene. Journal of Biological Chemistry, 268(24), 17883-17888.