|
|
 Previous Article | Table of Contents | Next Article 
Expression and regulation of Bcl-2, Bcl-xl, and Bax correlate with p53
status and sensitivity to apoptosis in childhood acute lymphoblastic
leukemia
HW Findley, L Gu, AM Yeager and M Zhou
Division of Pediatric Hematology/Oncology/Bone Marrow Transplantation,
Emory University School of Medicine, Atlanta, GA 30322, USA.
Bcl-2 and its homologue, Bcl-x1, encode membrane-associated proteins that
protect neoplastic cells from DNA damage-induced apoptosis, whereas Bax is
a Bcl-2 antagonist that promotes cell death. In the present study, we
examined the expression and regulation of these genes at both the mRNA and
protein level in 22 pediatric acute lymphoblastic leukemia (ALL) cell
lines, as well as their sensitivity to apoptosis after exposure to ionizing
radiation (IR). Eleven of 22 lines expressed wild-type (wt) p53, 4
expressed mutant p53, and 7 did not express p53 (p53-null). Nine of 22
(41%) lines expressed Bcl-2; of these, 8 were wt- p53+ and 1 expressed
mutant p53. Bcl-2 was not expressed in any p53- null lines. In contrast,
all 22 lines were positive for Bcl-x1 and Bax, although expression level
varied. Treatment with IR (10 Gy) induced both downregulation of Bcl-2 and
upregulation of Bax at 2 to 5 hours post-IR in 5 of 8 (63%) wt-p53+ lines,
leading to apoptosis. Conversely, lines that failed to both downregulate
Bcl-2 and upregulate Bax after IR were resistant to apoptosis. Although
levels of Bcl-x1 expression varied among the 22 lines, high levels of
Bcl-x1 were observed in 5 of 7 (71%) p53- lines. There were no obvious
changes in the expression of Bcl-x1 in these lines after IR. However, among
the p53-null lines, resistance to IR was observed only in those expressing
high levels of Bcl-x1. These results suggest that expression of Bcl-2 but
not Bcl-x1 is p53-dependent and that IR-induced downregulation of Bcl-2 and
upregulation of Bax occur in most wt-p53+ lines and are associated with
radiosensitivity. Furthermore, high-level expression of Bcl-x1 occurs
predominantly in p53-null lines and is associated with resistance to
IR-induced apoptosis in these lines, indicating differential expression and
regulation of Bcl-2 and Bcl-x1 in pediatric ALL.
Volume 89,
Issue 8,
pp. 2986-2993,
04/15/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. Xu, F. Fang, D. K. St. Clair, S. Josson, P. Sompol, I. Spasojevic, and W. H. St. Clair
Suppression of RelB-mediated manganese superoxide dismutase expression reveals a primary mechanism for radiosensitization effect of 1{alpha},25-dihydroxyvitamin D3 in prostate cancer cells
Mol. Cancer Ther.,
July 1, 2007;
6(7):
2048 - 2056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kubota, K. Kinoshita, K. Suetomi, A. Fujimori, and S. Takahashi
Mcl-1 Depletion in Apoptosis Elicited by Ionizing Radiation in Peritoneal Resident Macrophages of C3H Mice
J. Immunol.,
March 1, 2007;
178(5):
2923 - 2931.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G Van de Putte, R Holm, A K Lie, M Baekelandt, and G B Kristensen
Markers of apoptosis in stage IB squamous cervical carcinoma
J. Clin. Pathol.,
June 1, 2005;
58(6):
590 - 594.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Tonini, C. Gabellini, L. Bagella, G. D'Andrilli, V. Masciullo, G. Romano, G. Scambia, G. Zupi, and A. Giordano
pRb2/p130 Decreases Sensitivity to Apoptosis Induced by Camptothecin and Doxorubicin but not by Taxol
Clin. Cancer Res.,
December 1, 2004;
10(23):
8085 - 8093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. H. Sarkar and Y. Li
Indole-3-Carbinol and Prostate Cancer
J. Nutr.,
December 1, 2004;
134(12):
3493S - 3498S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Waxman and P. S. Schwartz
Harnessing Apoptosis for Improved Anticancer Gene Therapy
Cancer Res.,
December 15, 2003;
63(24):
8563 - 8572.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Zhou, L. Gu, H. W. Findley, R. Jiang, and W. G. Woods
PTEN Reverses MDM2-mediated Chemotherapy Resistance by Interacting with p53 in Acute Lymphoblastic Leukemia Cells
Cancer Res.,
October 1, 2003;
63(19):
6357 - 6362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-H. Wang, Z. Zhang, P. D. Burrows, H. Kubagawa, S. L. Bridges Jr, H. W. Findley, and M. D. Cooper
V(D)J recombinatorial repertoire diversification during intraclonal pro-B to B-cell differentiation
Blood,
February 1, 2003;
101(3):
1030 - 1037.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Zhou, L. Gu, F. Li, Y. Zhu, W. G. Woods, and H. W. Findley
DNA Damage Induces a Novel p53-Survivin Signaling Pathway Regulating Cell Cycle and Apoptosis in Acute Lymphoblastic Leukemia Cells
J. Pharmacol. Exp. Ther.,
October 1, 2002;
303(1):
124 - 131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. H. Igney and P. H. Krammer
Immune escape of tumors: apoptosis resistance and tumor counterattack
J. Leukoc. Biol.,
June 1, 2002;
71(6):
907 - 920.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. M. Zhou, B. C. Y. Wong, X. M. Fan, H. B. Zhang, M. C. M. Lin, H. F. Kung, D. M. Fan, and S. K. Lam
Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak
Carcinogenesis,
September 1, 2001;
22(9):
1393 - 1397.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Wieder, F. Essmann, A. Prokop, K. Schmelz, K. Schulze-Osthoff, R. Beyaert, B. Dorken, and P. T. Daniel
Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3
Blood,
March 1, 2001;
97(5):
1378 - 1387.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Karawajew, V. Ruppert, C. Wuchter, A. Kosser, M. Schrappe, B. Dorken, and W.-D. Ludwig
Inhibition of in vitro spontaneous apoptosis by IL-7 correlates with Bcl-2 up-regulation, cortical/mature immunophenotype, and better early cytoreduction of childhood T-cell acute lymphoblastic leukemia
Blood,
July 1, 2000;
96(1):
297 - 306.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Walczak, A. Bouchon, H. Stahl, and P. H. Krammer
Tumor Necrosis Factor-related Apoptosis-inducing Ligand Retains Its Apoptosis-inducing Capacity on Bcl-2- or Bcl-xL-overexpressing Chemotherapy-resistant Tumor Cells
Cancer Res.,
June 1, 2000;
60(11):
3051 - 3057.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Katzenellenbogen, S. B. Baylin, and J. G. Herman
Hypermethylation of the DAP-Kinase CpG Island Is a Common Alteration in B-Cell Malignancies
Blood,
June 15, 1999;
93(12):
4347 - 4353.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. Finucane, E. Bossy-Wetzel, N. J. Waterhouse, T. G. Cotter, and D. R. Green
Bax-induced Caspase Activation and Apoptosis via Cytochrome c Release from Mitochondria Is Inhibitable by Bcl-xL
J. Biol. Chem.,
January 22, 1999;
274(4):
2225 - 2233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Ohlsson, N. Kley, H. Werner, and D. LeRoith
p53 Regulates Insulin-Like Growth Factor-I (IGF-I) Receptor Expression and IGF-I-Induced Tyrosine Phosphorylation in an Osteosarcoma Cell Line: Interaction between p53 and Sp1
Endocrinology,
March 1, 1998;
139(3):
1101 - 1107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Kaufmann, J. E. Karp, P. A. Svingen, S. Krajewski, P. J. Burke, S. D. Gore, and J. C. Reed
Elevated Expression of the Apoptotic Regulator Mcl-1 at the Time of Leukemic Relapse
Blood,
February 1, 1998;
91(3):
991 - 1000.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
