| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Department of Internal Medicine I, University Hospital [P. M., C. B., M. B., M. R., K-H. H., A. M., H. F., G. A., T. M. G.], Department of Pharmacology [K. G.], and Department of Surgery I [G. L.], University of Ulm, 89081 Ulm, Germany; Department of Medicine B, Westfälische Wilhelms-Universität, D-48129 Münster, Germany [M. M. L.]; Department of Medicine IV, Medical Faculty Mannheim, University of Heidelberg at Mannheim, D-68167 Mannheim, Germany [M. L.]; and Department of Surgery I, Miyazaki Medical College, Miyazaki, 889-1601, Japan [T. I.]
Claudin-4 has been identified as an integral constituent of tight junctions and has been found to be highly expressed in pancreatic cancer. The aim of the present study was to elucidate the effect of claudin-4 on growth and metastatic potential in pancreatic cancer cells, as well as the regulation of claudin-4 by oncogenic pathways. Claudin-4 was stably overexpressed in SUIT-2 pancreatic cancer cells, and its effect on invasion and growth in vitro was examined by using two-chamber invasion assays, soft agar assays, and fluorescence-activated cell sorter analysis. Claudin-4 localization was characterized by light and electron microscopy, and pulmonary colonization was analyzed in vivo after injection of claudin-4 overexpressing cells into the tail vein of nude mice. Overexpression of claudin-4 was associated with significantly reduced invasive potential in vitro and inhibited colony formation in soft agar assays. In vivo, tail vein-injected claudin-4 overexpressing cells formed significantly less pulmonary metastases in comparison with mock-transfected cells. These effects were not caused by changes in proliferation, cell cycle progression, or matrix metalloproteinase gelatinolytic activity, but were paralleled by increased cell contact formation. Moreover, proinvasive transforming growth factor ß was able to down-regulate claudin-4 in PANC-1 cells. Inhibition of Ras signaling by using dominant-negative Ras and specific inhibitors of both downstream effectors mitogen-activated protein/extracellular signal-regulated kinase kinase and phosphatidylinositol 3'-kinase also decreased claudin-4 expression. Our findings identify claudin-4 as a potent inhibitor of the invasiveness and metastatic phenotype of pancreatic cancer cells, and as a target of the transforming growth factor ß and Ras/Raf/extracellular signal-regulated kinase pathways.
This article has been cited by other articles:
|
|
 |
|
  S.-R. Shiou, A. B. Singh, K. Moorthy, P. K. Datta, M. K. Washington, R. D. Beauchamp, and P. Dhawan Smad4 Regulates Claudin-1 Expression in a Transforming Growth Factor-{beta}-Independent Manner in Colon Cancer Cells Cancer Res., February 15, 2007; 67(4): 1571 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boireau, M. Buchert, M. S. Samuel, J. Pannequin, J. L. Ryan, A. Choquet, H. Chapuis, X. Rebillard, C. Avances, M. Ernst, et al. DNA-methylation-dependent alterations of claudin-4 expression in human bladder carcinoma Carcinogenesis, February 1, 2007; 28(2): 246 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lioni, P. Brafford, C. Andl, A. Rustgi, W. El-Deiry, M. Herlyn, and K. S.M. Smalley Dysregulation of Claudin-7 Leads to Loss of E-Cadherin Expression and the Increased Invasion of Esophageal Squamous Cell Carcinoma Cells Am. J. Pathol., February 1, 2007; 170(2): 709 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Osanai, M. Murata, N. Nishikiori, H. Chiba, T. Kojima, and N. Sawada Epigenetic Silencing of Occludin Promotes Tumorigenic and Metastatic Properties of Cancer Cells via Modulations of Unique Sets of Apoptosis-Associated Genes. Cancer Res., September 15, 2006; 66(18): 9125 - 9133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Rinker-Schaeffer, J. P. O'Keefe, D. R. Welch, and D. Theodorescu Metastasis Suppressor Proteins: Discovery, Molecular Mechanisms, and Clinical Application. Clin. Cancer Res., July 1, 2006; 12(13): 3882 - 3889. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Michl, B. Knobel, and J. Downward CUTL1 Is Phosphorylated by Protein Kinase A, Modulating Its Effects on Cell Proliferation and Motility J. Biol. Chem., June 2, 2006; 281(22): 15138 - 15144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Oku, E. Sasabe, E. Ueta, T. Yamamoto, and T. Osaki Tight Junction Protein Claudin-1 Enhances the Invasive Activity of Oral Squamous Cell Carcinoma Cells by Promoting Cleavage of Laminin-5 {gamma}2 Chain via Matrix Metalloproteinase (MMP)-2 and Membrane-Type MMP-1. Cancer Res., May 15, 2006; 66(10): 5251 - 5257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ebihara, M. Kondoh, N. Hasuike, M. Harada, H. Mizuguchi, Y. Horiguchi, M. Fujii, and Y. Watanabe Preparation of a Claudin-Targeting Molecule Using a C-Terminal Fragment of Clostridium perfringens Enterotoxin J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 255 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. N. Lee, E. Huang, and H. J. Ward Tight junction biology and kidney dysfunction Am J Physiol Renal Physiol, January 1, 2006; 290(1): F20 - F34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Fedwick, T. K. Lapointe, J. B. Meddings, P. M. Sherman, and A. G. Buret Helicobacter pylori Activates Myosin Light-Chain Kinase To Disrupt Claudin-4 and Claudin-5 and Increase Epithelial Permeability Infect. Immun., December 1, 2005; 73(12): 7844 - 7852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Morin Claudin Proteins in Human Cancer: Promising New Targets for Diagnosis and Therapy Cancer Res., November 1, 2005; 65(21): 9603 - 9606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Agarwal, T. D'Souza, and P. J. Morin Claudin-3 and Claudin-4 Expression in Ovarian Epithelial Cells Enhances Invasion and Is Associated with Increased Matrix Metalloproteinase-2 Activity Cancer Res., August 15, 2005; 65(16): 7378 - 7385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. De Craene, B. Gilbert, C. Stove, E. Bruyneel, F. van Roy, and G. Berx The Transcription Factor Snail Induces Tumor Cell Invasion through Modulation of the Epithelial Cell Differentiation Program Cancer Res., July 15, 2005; 65(14): 6237 - 6244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Barry, A. B. Nobel, and F. A. Wright Significance analysis of functional categories in gene expression studies: a structured permutation approach Bioinformatics, May 1, 2005; 21(9): 1943 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mima, S. Tsutsumi, H. Ushijima, M. Takeda, I. Fukuda, K. Yokomizo, K. Suzuki, K. Sano, T. Nakanishi, W. Tomisato, et al. Induction of Claudin-4 by Nonsteroidal Anti-inflammatory Drugs and Its Contribution to Their Chemopreventive Effect Cancer Res., March 1, 2005; 65(5): 1868 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Gadal, A Starzec, C Bozic, C Pillot-Brochet, S Malinge, V Ozanne, J Vicenzi, L Buffat, G Perret, F Iris, et al. Integrative analysis of gene expression patterns predicts specific modulations of defined cell functions by estrogen and tamoxifen in MCF7 breast cancer cells J. Mol. Endocrinol., February 1, 2005; 34(1): 61 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. T. Cheung, K. L. Leung, Y. C. Ip, X. Chen, D. Y. Fong, I. O. Ng, S. T. Fan, and S. So Claudin-10 Expression Level is Associated with Recurrence of Primary Hepatocellular Carcinoma Clin. Cancer Res., January 15, 2005; 11(2): 551 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Van Itallie and J. M. Anderson The Molecular Physiology of Tight Junction Pores Physiology, December 1, 2004; 19(6): 331 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Brumby, J. Secombe, J. Horsfield, M. Coombe, N. Amin, D. Coates, R. Saint, and H. Richardson A Genetic Screen for Dominant Modifiers of a cyclin E Hypomorphic Mutation Identifies Novel Regulators of S-Phase Entry in Drosophila Genetics, September 1, 2004; 168(1): 227 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Turksen and T.-C. Troy Barriers built on claudins J. Cell Sci., May 15, 2004; 117(12): 2435 - 2447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Steeg PERSPECTIVES ON CLASSIC ARTICLES: Metastasis Suppressor Genes J Natl Cancer Inst, March 17, 2004; 96(6): E4 - E4. [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 |
