|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2863-2870
Altered Expression and Activity of Topoisomerases During
All-Trans Retinoic Acid-Induced Differentiation of
HL-60 Cells
Masako Aoyama,
Dale R. Grabowski,
Richard J. Isaacs,
Kim A. Krivacic,
Lisa A. Rybicki,
Ronald M. Bukowski,
Mahrukh K. Ganapathi,
Ian D. Hickson, and
Ram Ganapathi
From the Experimental Therapeutics Program, Taussig Cancer Center,
Cleveland Clinic Foundation, Cleveland, OH; and the Molecular
Oncology Laboratory, ICRF Unit, John Radcliffe Hospital, Oxford,
UK.
Regulation of topoisomerase II (TOPO II) isozymes  and  is
influenced by the growth and transformation state of cells. Using HL-60
cells induced to differentiate by all-trans retinoic acid (RA),
we have investigated the expression and regulation of TOPO II isozymes
as well as the levels of topoisomerase I (TOPO I). During RA-induced
differentiation of human leukemia HL-60 cells, levels of TOPO I
remained unchanged, whereas the levels and phosphorylation of TOPO
II and TOPO II proteins were increased twofold to fourfold and
fourfold to eightfold, respectively. The elevation of TOPO II ( and
) protein levels and phosphorylation was apparent at 48 hours of
treatment with RA and persisted through 96 hours. The increased level
of TOPO II protein was also detected in differentiated cells
subsequently cultured for 96 hours in RA-free medium. Pulse chase
experiments in cells labeled with 35S-methionine showed
that the rate of degradation of TOPO II protein in control cells was
about twofold faster than that in the differentiated RA-treated cells.
The level of decatenation activity of kDNA was comparable in nuclear
extracts from control or RA-treated cells. Whereas etoposide (1 to 10 µmol/L) -induced DNA cleavage was not significantly different,
apoptosis was significantly lower (P = .012) in RA-treated
versus control cells after exposure to 10 µmol/L etoposide.
Consistent with unaltered levels of TOPO I, camptothecin (CPT) -induced
DNA cleavage was similar in control or RA-treated cells. However,
apoptosis after exposure to 1 to 10 µmol/L CPT was significantly
lower (P = .003 to P < .001) in RA-treated versus
control cells. Results suggest that TOPO II protein levels are
posttranscriptionally regulated and that degradation of TOPO II is
decreased during RA-induced differentiation. Furthermore, whereas the
total level of TOPO II ( + ) is increased with RA, the level of
TOPO II catalytic activity and etoposide-stabilized DNA cleavage
activity remains unaltered. Thus, TOPO II may have a specific role
in transcription of genes involved in differentiation with RA
treatment.
© 1998 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:
|
|
|
|
 
S. McNamara, H. Wang, N. Hanna, and W. H. Miller Jr.
Topoisomerase II{beta} Negatively Modulates Retinoic Acid Receptor {alpha} Function: a Novel Mechanism of Retinoic Acid Resistance
Mol. Cell. Biol.,
March 15, 2008;
28(6):
2066 - 2077.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-J. Kim and R. Lotan
Identification of Retinoid-Modulated Proteins in Squamous Carcinoma Cells Using High-Throughput Immunoblotting
Cancer Res.,
April 1, 2004;
64(7):
2439 - 2448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. U. Kurz, S. E. Wilson, K. B. Leader, B. P. Sampey, W. P. Allan, J. C. Yalowich, and D. J. Kroll
The Histone Deacetylase Inhibitor Sodium Butyrate Induces DNA Topoisomerase II{alpha} Expression and Confers Hypersensitivity to Etoposide in Human Leukemic Cell Lines
Mol. Cancer Ther.,
December 1, 2001;
1(2):
121 - 131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. van Stolk, G. Stoner, W. L. Hayton, K. Chan, B. DeYoung, L. Kresty, B. H. Kemmenoe, P. Elson, L. Rybicki, J. Church, et al.
Phase I Trial of Exisulind (Sulindac Sulfone, FGN-1) as a Chemopreventive Agent in Patients with Familial Adenomatous Polyposis
Clin. Cancer Res.,
January 1, 2000;
6(1):
78 - 89.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. R. Grabowski, K. A. Holmes, M. Aoyama, Y. Ye, L. A. Rybicki, R. M. Bukowski, M. K. Ganapathi, I. D. Hickson, and R. Ganapathi
Altered Drug Interaction and Regulation of Topoisomerase IIbeta : Potential Mechanisms Governing Sensitivity of HL-60 Cells to Amsacrine and Etoposide
Mol. Pharmacol.,
December 1, 1999;
56(6):
1340 - 1345.
[Abstract]
[Full Text]
|
|
|
|
|
