INHIBITION OF C-FES EXPRESSION BY AN ANTISENSE OLIGOMER CAUSES APOPTOSIS OF HL-60 CELLS INDUCED TO GRANULOCYTIC DIFFERENTIATION

被引:63
作者
MANFREDINI, R
GRANDE, A
TAGLIAFICO, E
BARBIERI, D
ZUCCHINI, P
CITRO, G
ZUPI, G
FRANCESCHI, C
TORELLI, U
FERRARI, S
机构
[1] UNIV MODENA, INST GEN PATHOL, I-41100 MODENA, ITALY
[2] REGINA ELENA TUMOR INST, EXPTL CHEMOTHERAPY LAB, I-00161 ROME, ITALY
关键词
D O I
10.1084/jem.178.2.381
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 HL60 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.
引用
收藏
页码:381 / 389
页数:9
相关论文
共 52 条
[41]   MACROPHAGE PHAGOCYTOSIS OF AGING NEUTROPHILS IN INFLAMMATION - PROGRAMMED CELL-DEATH IN THE NEUTROPHIL LEADS TO ITS RECOGNITION BY MACROPHAGES [J].
SAVILL, JS ;
WYLLIE, AH ;
HENSON, JE ;
WALPORT, MJ ;
HENSON, PM ;
HASLETT, C .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (03) :865-875
[42]  
SMITHGALL TE, 1988, J BIOL CHEM, V263, P15050
[43]   USE OF SYNTHETIC OLIGONUCLEOTIDES AS HYBRIDIZATION PROBES .3. ISOLATION OF CLONED CDNA SEQUENCES FOR HUMAN BETA-2-MICROGLOBULIN [J].
SUGGS, SV ;
WALLACE, RB ;
HIROSE, T ;
KAWASHIMA, EH ;
ITAKURA, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (11) :6613-6617
[44]  
VANDERKROL AR, 1988, BIOTECHNIQUES, V6, P958
[45]   INDUCTION OF DIFFERENTIATION IN HL-60 CELLS BY RETINOIC ACID AND LYMPHOCYTE-DERIVED DIFFERENTIATION-INDUCING FACTOR BUT NOT BY RECOMBINANT G-CSF AND GM-CSF [J].
WANG, SY ;
LIU, ST ;
WANG, SJ ;
HO, CK .
LEUKEMIA RESEARCH, 1989, 13 (12) :1091-1097
[46]   DIFFERENTIATION THERAPY OF ACUTE PROMYELOCYTIC LEUKEMIA WITH TRETINOIN (ALL-TRANS-RETINOIC ACID) [J].
WARRELL, RP ;
FRANKEL, SR ;
MILLER, WH ;
SCHEINBERG, DA ;
ITRI, LM ;
HITTELMAN, WN ;
VYAS, R ;
ANDREEFF, M ;
TAFURI, A ;
JAKUBOWSKI, A ;
GABRILOVE, J ;
GORDON, MS ;
DMITROVSKY, E .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (20) :1385-1393
[47]  
WEISS R, 1984, RNA TUMOR VIRUSES MO
[48]  
WILKS A F, 1990, Progress in Growth Factor Research, V2, P97, DOI 10.1016/0955-2235(90)90026-G
[49]   HEMATOPOIETIC COLONY STIMULATING FACTORS PROMOTE CELL-SURVIVAL BY SUPPRESSING APOPTOSIS [J].
WILLIAMS, GT ;
SMITH, CA ;
SPOONCER, E ;
DEXTER, TM ;
TAYLOR, DR .
NATURE, 1990, 343 (6253) :76-79
[50]   CHROMATIN CLEAVAGE IN APOPTOSIS - ASSOCIATION WITH CONDENSED CHROMATIN MORPHOLOGY AND DEPENDENCE ON MACROMOLECULAR-SYNTHESIS [J].
WYLLIE, AH ;
MORRIS, RG ;
SMITH, AL ;
DUNLOP, D .
JOURNAL OF PATHOLOGY, 1984, 142 (01) :67-77