Inhibition of c-fes expression by an antisense oligomer causes apoptosis of HL60 cells induced to granulocytic differentiation

Rossella Manfredini, Alexis Grande, Enrico Tagliafico, Daniela Barbieri, Patrizia Zucchini, Gennaro Citro, Gabriella Zupi, Claudio Franceschi, Umberto Torelli, Sergio Ferrari

Research output: Contribution to journalArticle

Abstract

The c-fes protooncogene is expressed at high levels in the terminal stages of granulocytic differentiation, but so far no definite function has been attributed to the product of this oncogene. To tackle this problem, the c-fes protooncogene expression has been inhibited in HIL60 cells, and fresh leukemic promyelocytes of acute promyelocytic leukemia have been induced to differentiate with retinoic acid (RA) and dimethylsulfoxide (DMSO). Inhibition was obtained by incubating the cells with a specific c-fes antisense oligodeoxynucleotide. It was observed that the cells, rather than differentiating, underwent premature cell death showing the morphological and molecular characteristics of apoptosis. This process was inhibited by granulocyte and granulocyte/macrophage colony-stimulating factor, but not by interleukin 3 (IL-3), IL-6, or stem cell factor. Our present results demonstrate that the loss of cell viability that occurs during the in vitro differentiation of myeloid cells, after the complete inhibition of the c-fes gene product and treatment with RA-DMSO, is due to activation of programmed cell death. It is concluded that a possible role of the c-fes gene product is to exert an antiapoptotic effect during granulocytic differentiation.

Original languageEnglish
Pages (from-to)381-389
Number of pages9
JournalJournal of Experimental Medicine
Volume178
Issue number2
Publication statusPublished - Aug 1 1993

    Fingerprint

ASJC Scopus subject areas

  • Immunology

Cite this

Manfredini, R., Grande, A., Tagliafico, E., Barbieri, D., Zucchini, P., Citro, G., Zupi, G., Franceschi, C., Torelli, U., & Ferrari, S. (1993). Inhibition of c-fes expression by an antisense oligomer causes apoptosis of HL60 cells induced to granulocytic differentiation. Journal of Experimental Medicine, 178(2), 381-389.