|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 1100-1107
Expression of the Death Gene Bik/Nbk Promotes Sensitivity to
Drug-Induced Apoptosis in Corticosteroid-Resistant T-Cell Lymphoma and
Prevents Tumor Growth in Severe Combined Immunodeficient Mice
Peter T. Daniel,
Kwok-Tao Pun,
Silke Ritschel,
Isrid Sturm,
Jutta Holler,
Bernd Dörken, and
Robin Brown
From the Max Delbrück Center for Molecular Medicine; the
Department of Hematology, Oncology and Tumor Immunology,
Charité Campus Berlin-Buch, Humboldt University, Berlin-Buch,
Germany; and the Cell Biology Unit, Glaxo Wellcome Medicines Research
Centre, Stevenage, United Kingdom.
Members of the Bcl-2 gene family have been implicated in the
regulation of cell death induced by cytostatic drugs. In some malignancies such as B-cell lymphoma, there is evidence that high expression of Bcl-2 is an independent negative prognostic marker and
the overexpression of Bcl-2 has been shown to confer resistance to
cytotoxic drugs by preventing drug-induced apoptosis. This function of
Bcl-2 can be antagonized by apoptosis-promoting members of the Bcl-2
family. We previously showed that overexpression of Bax restores the
chemosensitivity of Bax-deficient breast cancer cell lines. Therefore,
we investigated whether the death-promoting Bcl-2 homologue Bik/Nbk can
enhance cytostatic drug-induced apoptosis. As a model, we used the
T-cell leukemia H9 (CD3+ and
CD4+CD8 ), which is resistant to
corticosteroid-induced cell death and does not express endogenous
Bik/Nbk. Sensitivity for drug-induced apoptosis was increased 10- to
39-fold in cells transfected with the full-length coding sequence of
Bik/Nbk. In addition, apoptosis induced via CD95/Fas or heat shock was
increased to a similar extent. These data show that Bik/Nbk, which,
unlike Bax, carries only a BH3 but no BH1 or BH2 domain may be a target
to enhance chemosensitivity. The complete suppression of tumor growth
in a severe combined immunodeficient mouse xenotransplant model
suggests that, in analogy to Bax, Bik/Nbk may function as a tumor
suppressor gene.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Gillissen, F. Essmann, P. G. Hemmati, A. Richter, A. Richter, I. Oztop, G. Chinnadurai, B. Dorken, and P. T. Daniel
Mcl-1 determines the Bax dependency of Nbk/Bik-induced apoptosis
J. Cell Biol.,
November 19, 2007;
179(4):
701 - 715.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Benito, O. Gutierrez, C. Pipaon, P. J. Real, F. Gachon, A. E. Ritchie, and J. L. Fernandez-Luna
A Novel Role for Proline- and Acid-rich Basic Region Leucine Zipper (PAR bZIP) Proteins in the Transcriptional Regulation of a BH3-only Proapoptotic Gene
J. Biol. Chem.,
December 15, 2006;
281(50):
38351 - 38357.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Hur, J. Chesnes, K. R. Coser, R. S. Lee, P. Geck, K. J. Isselbacher, and T. Shioda
The Bik BH3-only protein is induced in estrogen-starved and antiestrogen-exposed breast cancer cells and provokes apoptosis
PNAS,
February 24, 2004;
101(8):
2351 - 2356.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. M. Li, Y. Wen, B. P. Zhou, H.-P. Kuo, Q. Ding, and M.-C. Hung
Enhancement of Bik Antitumor Effect by Bik Mutants
Cancer Res.,
November 15, 2003;
63(22):
7630 - 7633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Jiang and E. A. Clark
Involvement of Bik, a Proapoptotic Member of the Bcl-2 Family, in Surface IgM-Mediated B Cell Apoptosis
J. Immunol.,
May 15, 2001;
166(10):
6025 - 6033.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Sturm, H. Petrowsky, R. Volz, M. Lorenz, S. Radetzki, T. Hillebrand, G. Wolff, S. Hauptmann, B. Dorken, and P. T. Daniel
Analysis of p53/BAX/p16ink4a/CDKN2 in Esophageal Squamous Cell Carcinoma: High BAX and p16ink4a/CDKN2 Identifies Patients With Good Prognosis
J. Clin. Oncol.,
April 15, 2001;
19(8):
2272 - 2281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Marshansky, X. Wang, R. Bertrand, H. Luo, W. Duguid, G. Chinnadurai, N. Kanaan, M. D. Vu, and J. Wu
Proteasomes Modulate Balance Among Proapoptotic and Antiapoptotic Bcl-2 Family Members and Compromise Functioning of the Electron Transport Chain in Leukemic Cells
J. Immunol.,
March 1, 2001;
166(5):
3130 - 3142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
