| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
B Activity and Chemoresistance in Pancreatic Carcinoma Cell Lines1
Laboratory of Molecular Gastroenterology, Department of Medicine, University of Kiel, D-24105 Kiel, Germany [A. A., J. V., S. M., U. R. F., H. S.], and Department of Medicine I, St. Josef Hospital, Ruhr-University of Bochum, D-44791 Bochum, Germany [H. Y., W. E. S.]
We have recently shown that several pancreatic carcinoma cell lines are resistant to topoisomerase II
inhibitors due to elevated basal nuclear factor 
B (NF-B) activity, and blockade of this activity by various means strongly increased chemosensitivity. In search of possible mechanisms leading to exaggerated NF-B activity, we identified interleukin (IL)-1ß as a key mediator of this activation in two of the chemoresistant cell lines (A818-4 and PancTu-1). These cells express and secrete high levels of IL-1ß, as demonstrated by reverse transcription-PCR, immunocytochemistry, and ELISA. Culture supernatants from both cell lines induced NF-B activity in chemosensitive PT45-P1 pancreatic carcinoma cells and significantly attenuated etoposide-induced apoptosis in a NF-B-dependent fashion, similar to that seen in PT45-P1 cells treated with recombinant IL-1ß. Treatment of these cells with IL-1ß also changed the DNA damage characteristics toward those observed in A818-4 and PancTu-1 cells. NF-B activation and the gain of chemoresistance in PT45-P1 cells on treatment with supernatants from both chemoresistant cell lines was abolished in the presence of a blocking anti-IL-1 receptor (I) antibody. Furthermore, this antibody decreased the resistance of A818-4 and PancTu-1 cells to etoposide treatment along with reduced NF-B activity. Blockade of NF-B activation by MG132, sulfasalazine, or an IB superrepressor disrupted the IL-1ß-mediated amplification loop and the accompanying chemoresistance. Our data provide insights into an autocrine mechanism involving IL-1ß by which pancreatic carcinoma cells develop chemoresistance that could serve as a molecular target in anticancer therapy.
This article has been cited by other articles:
|
|
 |
|
  T. Copetti, C. Bertoli, E. Dalla, F. Demarchi, and C. Schneider p65/RelA Modulates BECN1 Transcription and Autophagy Mol. Cell. Biol., May 15, 2009; 29(10): 2594 - 2608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shin, T. Asano, Y. Yao, R. Zhang, F.-X. Claret, M. Korc, K. Sabapathy, D. G. Menter, J. L. Abbruzzese, and S. A.G. Reddy Activator Protein-1 Has an Essential Role in Pancreatic Cancer Cells and Is Regulated by a Novel Akt-Mediated Mechanism Mol. Cancer Res., May 1, 2009; 7(5): 745 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-D. Lay, C.-C. Hong, J.-S. Huang, Y.-Y. Yang, C.-Y. Pao, C.-H. Liu, Y.-P. Lai, G.-M. Lai, A.-L. Cheng, I.-J. Su, et al. Sulfasalazine Suppresses Drug Resistance and Invasiveness of Lung Adenocarcinoma Cells Expressing AXL Cancer Res., April 15, 2007; 67(8): 3878 - 3887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nakashima, M. Nakamura, H. Yamaguchi, N. Yamanaka, T. Akiyoshi, K. Koga, K. Yamaguchi, M. Tsuneyoshi, M. Tanaka, and M. Katano Nuclear Factor-{kappa}B Contributes to Hedgehog Signaling Pathway Activation through Sonic Hedgehog Induction in Pancreatic Cancer. Cancer Res., July 15, 2006; 66(14): 7041 - 7049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-T. Lin, C.-Y. Zuon, C.-C. Chang, S.-T. Chen, C.-P. Chen, B.-R. Lin, M.-Y. Wang, Y.-M. Jeng, K.-J. Chang, P.-H. Lee, et al. Cyr61 Induces Gastric Cancer Cell Motility/Invasion via Activation of the Integrin/Nuclear Factor-{kappa}B/Cyclooxygenase-2 Signaling Pathway Clin. Cancer Res., August 15, 2005; 11(16): 5809 - 5820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Takahashi, S. Kobayashi, S. Kajino, K. Imai, K. Tomoda, S. Shimizu, and T. Okamoto Inhibition of the 53BP2S-mediated apoptosis by nuclear factor {kappa}B and Bcl-2 family proteins Genes Cells, August 1, 2005; 10(8): 803 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Till, P. Rosenstiel, A. Krippner-Heidenreich, S. Mascheretti-Croucher, P. J. P. Croucher, H. Schafer, P. Scheurich, D. Seegert, and S. Schreiber The Met-196 -> Arg Variation of Human Tumor Necrosis Factor Receptor 2 (TNFR2) Affects TNF-{alpha}-induced Apoptosis by Impaired NF-{kappa}B Signaling and Target Gene Expression J. Biol. Chem., February 18, 2005; 280(7): 5994 - 6004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Muerkoster, A. Arlt, B. Sipos, M. Witt, M. Grossmann, G. Kloppel, H. Kalthoff, U. R. Folsch, and H. Schafer Increased Expression of the E3-Ubiquitin Ligase Receptor Subunit {beta}TRCP1 Relates to Constitutive Nuclear Factor-{kappa}B Activation and Chemoresistance in Pancreatic Carcinoma Cells Cancer Res., February 15, 2005; 65(4): 1316 - 1324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Robe, M. Bentires-Alj, M. Bonif, B. Rogister, M. Deprez, H. Haddada, M.-T. N. Khac, O. Jolois, K. Erkmen, M.-P. Merville, et al. In vitro and In vivo Activity of the Nuclear Factor-{kappa}B Inhibitor Sulfasalazine in Human Glioblastomas Clin. Cancer Res., August 15, 2004; 10(16): 5595 - 5603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Niu, Z. Li, B. Peng, and P. J. Chiao Identification of an Autoregulatory Feedback Pathway Involving Interleukin-1{alpha} in Induction of Constitutive NF-{kappa}B Activation in Pancreatic Cancer Cells J. Biol. Chem., April 16, 2004; 279(16): 16452 - 16462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Yamanaka, T. Morisaki, H. Nakashima, A. Tasaki, M. Kubo, H. Kuga, C. Nakahara, K. Nakamura, H. Noshiro, T. Yao, et al. Interleukin 1{beta} Enhances Invasive Ability of Gastric Carcinoma through Nuclear Factor-{kappa}B Activation Clin. Cancer Res., March 1, 2004; 10(5): 1853 - 1859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Muerkoster, K. Wegehenkel, A. Arlt, M. Witt, B. Sipos, M.-L. Kruse, T. Sebens, G. Kloppel, H. Kalthoff, U. R. Folsch, et al. Tumor Stroma Interactions Induce Chemoresistance in Pancreatic Ductal Carcinoma Cells Involving Increased Secretion and Paracrine Effects of Nitric Oxide and Interleukin-1{beta} Cancer Res., February 15, 2004; 64(4): 1331 - 1337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Sathe, N. Sizemore, X. Li, K. Vithalani, M. Commane, S. M. Swiatkowski, and G. R. Stark Mutant human cells with constitutive activation of NF-{kappa}B PNAS, January 6, 2004; 101(1): 192 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Monti, B. E. Leone, F. Marchesi, G. Balzano, A. Zerbi, F. Scaltrini, C. Pasquali, G. Calori, F. Pessi, C. Sperti, et al. The CC Chemokine MCP-1/CCL2 in Pancreatic Cancer Progression: Regulation of Expression and Potential Mechanisms of Antimalignant Activity Cancer Res., November 1, 2003; 63(21): 7451 - 7461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. F. Zerbini, Y. Wang, J.-Y. Cho, and T. A Libermann Constitutive Activation of Nuclear Factor {kappa}B p50/p65 and Fra-1 and JunD Is Essential for Deregulated Interleukin 6 Expression in Prostate Cancer Cancer Res., May 1, 2003; 63(9): 2206 - 2215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Bayon, M. A. Ortiz, F. J. Lopez-Hernandez, F. Gao, M. Karin, M. Pfahl, and F. J. Piedrafita Inhibition of I{kappa}B Kinase by a New Class of Retinoid-Related Anticancer Agents That Induce Apoptosis Mol. Cell. Biol., February 1, 2003; 23(3): 1061 - 1074. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
