LYMPHOMA MODELS FOR B-CELL ACTIVATION AND TOLERANCE .10. ANTI-MU-MEDIATED GROWTH ARREST AND APOPTOSIS OF MURINE B-CELL LYMPHOMAS IS PREVENTED BY THE STABILIZATION OF MYC

被引:110
作者
FISCHER, G
KENT, SC
JOSEPH, L
GREEN, DR
SCOTT, DW
机构
[1] UNIV ROCHESTER,CTR CANC,DIV IMMUNOL,ROCHESTER,NY 14642
[2] UNIV ROCHESTER,SCH MED & DENT,DEPT MICROBIOL & IMMUNOL,ROCHESTER,NY 14642
[3] LA JOLLA INST ALLERGY & IMMUNOL,LA JOLLA,CA 92037
关键词
D O I
10.1084/jem.179.1.221
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Treatment of the WEHI-2131 or CH31 B cell lymphomas with anti-mu or transforming growth factor (TGF)-beta leads to growth inhibition and subsequent cell death via apoptosis. Since anti-mu stimulates a transient increase in c-myc and c-fos transcription in these lymphomas, we examined the role of these proteins in growth regulation using antisense oligonucleotides. Herein, we demonstrate that antisense oligonucleotides for c-myc prevent both anti-mu- and TGF-beta-mediated growth inhibiiton in the CH31 and WEHI-231 B cell lymphomas, whereas antisense c-fos has no effect. Furthermore, antisense c-myc promotes the appearance of phosphorylated retinoblastoma protein in the presence of anti-mu and prevents the progression to apoptosis as measured by propidium iodide staining. Northern and Western analyses show that c-myc message and the levels of multiple myc proteins were maintained in the presence of antisense c-myc, results indicating that myc species are critical for the continuation of proliferation and the prevention of apoptosis. These data implicate c-myc in the negative signaling pathway of both TGF-beta and anti-mu.
引用
收藏
页码:221 / 228
页数:8
相关论文
共 33 条
[1]   THE C-MYC ONCOGENE DRIVEN BY IMMUNOGLOBULIN ENHANCERS INDUCES LYMPHOID MALIGNANCY IN TRANSGENIC MICE [J].
ADAMS, JM ;
HARRIS, AW ;
PINKERT, CA ;
CORCORAN, LM ;
ALEXANDER, WS ;
CORY, S ;
PALMITER, RD ;
BRINSTER, RL .
NATURE, 1985, 318 (6046) :533-538
[2]   A BLOCK TO ELONGATION IS LARGELY RESPONSIBLE FOR DECREASED TRANSCRIPTION OF C-MYC IN DIFFERENTIATED HL60 CELLS [J].
BENTLEY, DL ;
GROUDINE, M .
NATURE, 1986, 321 (6071) :702-706
[3]   INHIBITORY EFFECTS OF ANTISENSE OLIGODEOXYNUCLEOTIDES TARGETING C-MYC MESSENGER-RNA ON SMOOTH-MUSCLE CELL-PROLIFERATION AND MIGRATION [J].
BIRO, S ;
FU, YM ;
YU, ZX ;
EPSTEIN, SE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (02) :654-658
[4]  
BISONETTE RP, 1992, NATURE, V359, P552
[5]   THE RETINOBLASTOMA PROTEIN IS PHOSPHORYLATED DURING SPECIFIC PHASES OF THE CELL-CYCLE [J].
BUCHKOVICH, K ;
DUFFY, LA ;
HARLOW, E .
CELL, 1989, 58 (06) :1097-1105
[6]   PHOSPHORYLATION OF THE RETINOBLASTOMA GENE-PRODUCT IS MODULATED DURING THE CELL-CYCLE AND CELLULAR-DIFFERENTIATION [J].
CHEN, PL ;
SCULLY, P ;
SHEW, JY ;
WANG, JYJ ;
LEE, WH .
CELL, 1989, 58 (06) :1193-1198
[7]   THYMOCYTE APOPTOSIS INDUCED BY P53-DEPENDENT AND INDEPENDENT PATHWAYS [J].
CLARKE, AR ;
PURDIE, CA ;
HARRISON, DJ ;
MORRIS, RG ;
BIRD, CC ;
HOOPER, ML ;
WYLLIE, AH .
NATURE, 1993, 362 (6423) :849-852
[8]   HUMAN C-MYC ONC GENE IS LOCATED ON THE REGION OF CHROMOSOME-8 THAT IS TRANSLOCATED IN BURKITT-LYMPHOMA CELLS [J].
DALLAFAVERA, R ;
BREGNI, M ;
ERIKSON, J ;
PATTERSON, D ;
GALLO, RC ;
CROCE, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (24) :7824-7827
[9]   INDUCTION OF APOPTOSIS IN FIBROBLASTS BY C-MYC PROTEIN [J].
EVAN, GI ;
WYLLIE, AH ;
GILBERT, CS ;
LITTLEWOOD, TD ;
LAND, H ;
BROOKS, M ;
WATERS, CM ;
PENN, LZ ;
HANCOCK, DC .
CELL, 1992, 69 (01) :119-128
[10]   ABROGATION BY C-MYC OF G1 PHASE ARREST INDUCED BY RB PROTEIN BUT NOT BY P53 [J].
GOODRICH, DW ;
LEE, WH .
NATURE, 1992, 360 (6400) :177-179