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

    Research output: Contribution to journalArticle

    57 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 - Jan 1 1993

      Fingerprint

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    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.