HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 1, 319-328, January 5, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/1/319    most recent M608065200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Song, J. J. Articles by Lee, Y. J. Search for Related Content PubMed PubMed Citation Articles by Song, J. J. Articles by Lee, Y. J. Social Bookmarking                      What's this?

Evidence for Two Modes of Development of Acquired Tumor Necrosis Factor-related Apoptosis-inducing Ligand Resistance

INVOLVEMENT OF Bcl-xL^*

Jae J. Song, Jee Young An, Yong Tae Kwon, and Yong J. Lee¹

From the Department of Surgery and Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213 and Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261

Previous studies have shown that repeated application of TRAIL induces acquired resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Using human prostate adenocarcinoma DU-145 and human pancreatic carcinoma MiaPaCa-2 cells as a model, we now demonstrate for the first time that two states of acquired TRAIL resistance can be developed after TRAIL treatment. Data from survival assay and Western blot analysis show that acquired TRAIL resistance was developed within 1 day and gradually decayed within 6 days after TRAIL treatment in both cell lines. After TRAIL treatment, the level of Bcl-xL increased and reached a maximum within 2 days and gradually decreased in both cell lines. Bcl-xL-mediated development of acquired TRAIL resistance was suppressed by knockdown of Bcl-xL expression. Protein interaction assay revealed that during the development of TRAIL resistance, Bcl-xL dissociated from Bad and then associated with Bax. Overexpression of mutant-type Bad (S136A), which prevents this dissociation, partially suppressed the development of acquired TRAIL resistance. Thus, our results suggest that (a) dissociation of Bad from Bcl-xL and (b) an increase in the intracellular level of Bcl-xL are responsible for development of acquired TRAIL resistance.

Received for publication, August 22, 2006 , and in revised form, November 13, 2006.

^* This work was supported by NCI, National Institutes of Health Grants CA95191, CA96989, and CA121395, Department of Defense Prostate Cancer Research Program Fund PC020530 Grant, and by the Susan G. Komen Breast Cancer Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Surgery, University of Pittsburgh, Hillman Cancer Center, 5117 Centre Ave., Rm. 1.46C, Pittsburgh, PA 15213. Tel.: 412-623-3268; Fax: 412-623-7709; E-mail: leeyj{at}upmc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Kato, A. Sadarangani, S. Lange, A. M. Delpiano, M. Vargas, J. Branes, J. Carvajal, S. Lipkowitz, G. I. Owen, and M. A. Cuello 2-Methoxyestradiol Mediates Apoptosis Through Caspase-Dependent and Independent Mechanisms in Ovarian Cancer Cells But Not in Normal Counterparts Reproductive Sciences, November 1, 2008; 15(9): 878 - 894. [Abstract] [PDF]

				C. Wilson, T. Wilson, P. G. Johnston, D. B. Longley, and D. J.J. Waugh Interleukin-8 signaling attenuates TRAIL- and chemotherapy-induced apoptosis through transcriptional regulation of c-FLIP in prostate cancer cells Mol. Cancer Ther., September 1, 2008; 7(9): 2649 - 2661. [Abstract] [Full Text] [PDF]

				M. Travert, P. Ame-Thomas, C. Pangault, A. Morizot, O. Micheau, G. Semana, T. Lamy, T. Fest, K. Tarte, and T. Guillaudeux CD40 Ligand Protects from TRAIL-Induced Apoptosis in Follicular Lymphomas through NF-{kappa}B Activation and Up-Regulation of c-FLIP and Bcl-xL J. Immunol., July 15, 2008; 181(2): 1001 - 1011. [Abstract] [Full Text] [PDF]

				X. Wang, W. Chen, W. Zeng, L. Bai, Y. Tesfaigzi, S. A. Belinsky, and Y. Lin Akt-mediated eminent expression of c-FLIP and Mcl-1 confers acquired resistance to TRAIL-induced cytotoxicity to lung cancer cells Mol. Cancer Ther., May 1, 2008; 7(5): 1156 - 1163. [Abstract] [Full Text] [PDF]

				B. S. Prabhakar, N. Mulherkar, and K. V. Prasad Role of IG20 Splice Variants in TRAIL Resistance Clin. Cancer Res., January 15, 2008; 14(2): 347 - 351. [Abstract] [Full Text] [PDF]