Abstract
In A549 human lung adenocarcinoma cells, we found that TNF-α and several commonly used chemotherapeutic agents upregulated the expression of Bcl-x and/or Bfl-1/A1 through an NF-κB-dependent pathway. While parental A549 cells were resistant to the cytotoxic effects of both TNF-α and chemotherapy agents, NF-κB-blocked A549 cells were sensitized to both. Expression of either Bcl-x or Bfl-1/A1 in the NF-κB-deficient cells at physiological levels provided differential protection against TNF-α and chemotherapeutic treatment. These studies provide a potential mechanism for the phenomenon of chemotherapy-induced chemoresistance, and also reveal a potential strategy by which chemoresistance can be overcome.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ashkenazi A and Dixit V. . 1998 Science 281: 1305–1308.
Beg AA and Baltimore D. . 1996 Science 274: 782–784.
Chu Z, McKinsey T, Liu L, Gentry J, Malim M and Ballard D. . 1997 Proc. Natl. Acad. Sci. USA 94: 10057–10062.
Grumont R, Rourke I and Gerondakis S. . 1999 Genes Dev. 13: 400–411.
Hsu H, Shu H, Pan M and Goeddel D. . 1996 Cell 94: 299–308.
Hsu H, Xiong J and Goeddel DV. . 1995 Cell 81: 495–504.
Lee H, Dadgostar H, Cheng Q, Shu J and Cheng G. . 1999a Proc. Natl. Acad. Sci. USA 96: 9136–9141.
Lee H, Dempsey P, Parks T, Zhu X, Baltimore D and Cheng G. . 1999b Proc. Natl. Acad. Sci. USA 96: 1421–1426.
Li H, ZH, Xu CJ and Yuan J. . 1998 Cell 94: 491–501.
Liu Z, Hsu H, Goeddel D and Karin M. . 1997 Cell 87: 565–576.
Luo X, Budihardjo I, Zou H, Slaughter C and Wang X. . 1998 Cell 94: 481–490.
Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli K, Debatin K, Krammer P and Peter M. . 1998 EMBO J. 17: 1675–1687.
Smith CA, Farrah T and Goodwin RG. . 1994 Cell 76: 959–962.
Stehlik C, de Martin R, Kumabashiri I, Schmid J, Binder, B and Lipp J. . 1998 J. Exp. Med. 188: 211–216.
Tamatani M, Che Y, Matsuzaki H, Ogawa S, Okado H, Miyake S, Mizuno T and Tohyama M. . 1999 J. Biol. Chem. 274: 8531–8538.
Van Antwerp D, Martin S, Kafri T, Green D and Verma, I. . 1996 Science 274: 787–789.
Wang C, Guttridge D, Mayo M and Baldwin AJ. . 1999 Mol. Cell. Biol. 19: 5923–5929.
Wang C, Mayo M, Korneluk R, Goeddel D and Baldwin AJ. . 1998 Science 281: 1680–1683.
Wang C-Y, Mayo MW and Baldwin AS. . 1996 Science 274: 784–787.
Wu M, Ao Z, Prasad K, Wu R and Schlossman S. . 1998 Science 281: 998–1001.
Zong W, Edelstein L, Chen C, Bash J and Gelinas C. . 1999 Genes Dev. 13: 382–387.
Acknowledgements
HH Lee is supported by a UCLA MSTP Training Grant (GM 08042).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cheng, Q., Lee, H., Li, Y. et al. Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-κB inhibition. Oncogene 19, 4936–4940 (2000). https://doi.org/10.1038/sj.onc.1203861
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203861
Keywords
This article is cited by
-
Integrated analysis of patient samples identifies biomarkers for venetoclax efficacy and combination strategies in acute myeloid leukemia
Nature Cancer (2020)
-
NFκBP65 transcription factor modulates resistance to doxorubicin through ABC transporters in breast cancer
Breast Cancer (2017)
-
Cisplatin Inhibits Hippocampal Cell Proliferation and Alters the Expression of Apoptotic Genes
Neurotoxicity Research (2014)
-
BCL2A1: the underdog in the BCL2 family
Cell Death & Differentiation (2012)
-
The C-terminal region of Bfl-1 sensitizes non-small cell lung cancer to gemcitabine-induced apoptosis by suppressing NF-κB activity and down-regulating Bfl-1
Molecular Cancer (2011)
