| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Medicine and Biological Chemistry, Division of Endocrinology and Metabolism, University of California, Irvine, California 92717 [M. E., M. Y., M. K.], and Department of Visceral and Transplantation Surgery, University of Berne, Inselspital, CH-3010 Berne, Switzerland [H. F., M. W. B.]
The c-met proto-oncogene encodes a transmembrane tyrosine kinase receptor (MET) that has the capacity to modulate cell proliferation and differentiation; it is activated by the hepatocyte growth factor. Using a highly specific anti-MET antibody we found mild MET immunoreactivity in acinar, ductal, and islet cells in the normal human pancreas and intense MET immunoreactivity in many of the duct-like cancer cells in 14 of 16 human pancreatic adenocarcinomas. Intense MET immunoreactivity was also evident in the ductal cells in regions adjacent to the cancer cells. Northern blot analysis of total RNA revealed that, by comparison with the normal pancreas, pancreatic cancers exhibited a 7-fold (P < 0.01) increase in c-met mRNA levels. Hepatocyte growth factor mRNA levels were increased 10-fold (P < 0.05) in the same cancers. The concomitant over-expression of c-met and hepatocyte growth factor in human pancreatic cancers suggests that there is excessive activation of c-met-dependent signaling pathways that may contribute to pancreatic cancer cell growth in vivo.
1 This study was supported by USPHS Grant CA-40162 awarded by the NIH to M. K.
2 Supported by Grant 2.93.43 awarded by the Gottlieb Daimler- and Karl Benz-Stiftung (Ladenburg, Germany) to M. E.
3 To whom requests for reprints should be addressed, at Division of Endocrinology and Metabolism, Medical Sciences I, C240, University of California, Irvine, CA 92717.
Received 9/ 1/94. Accepted 10/ 3/94.
This article has been cited by other articles:
|
|
 |
|
  H. Jin, R. Yang, Z. Zheng, M. Romero, J. Ross, H. Bou-Reslan, R. A.D. Carano, I. Kasman, E. Mai, J. Young, et al. MetMAb, the One-Armed 5D5 Anti-c-Met Antibody, Inhibits Orthotopic Pancreatic Tumor Growth and Improves Survival Cancer Res., June 1, 2008; 68(11): 4360 - 4368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Matsushita, T. Gotze, and M. Korc Hepatocyte Growth Factor Mediated Cell Invasion in Pancreatic Cancer Cells Is Dependent on Neuropilin-1 Cancer Res., November 1, 2007; 67(21): 10309 - 10316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zhao, T. Grabinski, C. Gao, R. S. Skinner, T. Giambernardi, Y. Su, E. Hudson, J. Resau, M. Gross, G. F. Vande Woude, et al. Identification of a Met-Binding Peptide from a Phage Display Library Clin. Cancer Res., October 15, 2007; 13(20): 6049 - 6055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Hoffmann, J. A. Tapia, M. J. Berna, M. Thill, T. Braunschweig, S. A. Mantey, T. W. Moody, and R. T. Jensen Gastrointestinal Hormones Cause Rapid c-Met Receptor Down-regulation by a Novel Mechanism Involving Clathrin-mediated Endocytosis and a Lysosome-dependent Mechanism J. Biol. Chem., December 8, 2006; 281(49): 37705 - 37719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Heidenblad, E. F. P. M. Schoenmakers, T. Jonson, L. Gorunova, J. A. Veltman, A. G. van Kessel, and M. Hoglund Genome-Wide Array-Based Comparative Genomic Hybridization Reveals Multiple Amplification Targets and Novel Homozygous Deletions in Pancreatic Carcinoma Cell Lines Cancer Res., May 1, 2004; 64(9): 3052 - 3059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ohuchida, K. Mizumoto, M. Murakami, L.-W. Qian, N. Sato, E. Nagai, K. Matsumoto, T. Nakamura, and M. Tanaka Radiation to Stromal Fibroblasts Increases Invasiveness of Pancreatic Cancer Cells through Tumor-Stromal Interactions Cancer Res., May 1, 2004; 64(9): 3215 - 3222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Manabe, K. Mizumoto, E. Nagai, K. Matsumoto, T. Nakamura, T. Nukiwa, M. Tanaka, and T. Matsuda Cell-based Protein Delivery System for the Inhibition of the Growth of Pancreatic Cancer: NK4 Gene-transduced Oral Mucosal Epithelial Cell Sheet Clin. Cancer Res., August 1, 2003; 9(8): 3158 - 3166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sato, A. Maitra, N. Fukushima, N. T. van Heek, H. Matsubayashi, C. A. Iacobuzio-Donahue, C. Rosty, and M. Goggins Frequent Hypomethylation of Multiple Genes Overexpressed in Pancreatic Ductal Adenocarcinoma Cancer Res., July 15, 2003; 63(14): 4158 - 4166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Herynk, O. Stoeltzing, N. Reinmuth, N. U. Parikh, R. Abounader, J. Laterra, R. Radinsky, L. M. Ellis, and G. E. Gallick Down-Regulation of c-Met Inhibits Growth in the Liver of Human Colorectal Carcinoma Cells Cancer Res., June 1, 2003; 63(11): 2990 - 2996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. L. H. van Leenders, W. R. Gage, J. L. Hicks, B. van Balken, T. W. Aalders, J. A. Schalken, and A. M. De Marzo Intermediate Cells in Human Prostate Epithelium Are Enriched in Proliferative Inflammatory Atrophy Am. J. Pathol., May 1, 2003; 162(5): 1529 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Peghini, M. Iwamoto, M. Raffeld, Y.-J. Chen, S. U. Goebel, J. Serrano, and R. T. Jensen Overexpression of Epidermal Growth Factor and Hepatocyte Growth Factor Receptors in a Proportion of Gastrinomas Correlates with Aggressive Growth and Lower Curability Clin. Cancer Res., July 1, 2002; 8(7): 2273 - 2285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-N. Qian, X. Guo, B. Cao, E. J. Kort, C.-C. Lee, J. Chen, L.-M. Wang, W.-Y. Mai, H.-Q. Min, M.-H. Hong, et al. Met Protein Expression Level Correlates with Survival in Patients with Late-stage Nasopharyngeal Carcinoma Cancer Res., January 1, 2002; 62(2): 589 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tomioka, N. Maehara, K. Kuba, K. Mizumoto, M. Tanaka, K. Matsumoto, and T. Nakamura Inhibition of Growth, Invasion, and Metastasis of Human Pancreatic Carcinoma Cells by NK4 in an Orthotopic Mouse Model Cancer Res., October 1, 2001; 61(20): 7518 - 7524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Watanabe, Y Oda, S Tamiya, K Masuda, and M Tsuneyoshi Malignant peripheral nerve sheath tumour arising within neurofibroma. An immunohistochemical analysis in the comparison between benign and malignant components J. Clin. Pathol., August 1, 2001; 54(8): 631 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Matsuda, H. Maruyama, F. Guo, J. Kleeff, J. Itakura, Y. Matsumoto, A. D. Lander, and M. Korc Glypican-1 Is Overexpressed in Human Breast Cancer and Modulates the Mitogenic Effects of Multiple Heparin-binding Growth Factors in Breast Cancer Cells Cancer Res., July 1, 2001; 61(14): 5562 - 5569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ohnami, N. Matsumoto, M. Nakano, K. Aoki, K. Nagasaki, T. Sugimura, M. Terada, and T. Yoshida Identification of Genes Showing Differential Expression in Antisense K-ras-transduced Pancreatic Cancer Cells with Suppressed Tumorigenicity Cancer Res., November 1, 1999; 59(21): 5565 - 5571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Paciucci, M. R. Vila, T. Adell, V. M. Diaz, M. Tora, T. Nakamura, and F. X. Real Activation of the Urokinase Plasminogen Activator/Urokinase Plasminogen Activator Receptor System and Redistribution of E-Cadherin Are Associated with Hepatocyte Growth Factor-Induced Motility of Pancreas Tumor Cells Overexpressing Met Am. J. Pathol., July 1, 1998; 153(1): 201 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Liu, T. Furukawa, M. Kobari, and M.-S. Tsao Comparative Phenotypic Studies of Duct Epithelial Cell Lines Derived from Normal Human Pancreas and Pancreatic Carcinoma Am. J. Pathol., July 1, 1998; 153(1): 263 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Borset, E. Lien, T. Espevik, E. Helseth, A. Waage, and A. Sundan Concomitant Expression of Hepatocyte Growth Factor/Scatter Factor and the Receptor c-MET in Human Myeloma Cell Lines J. Biol. Chem., October 4, 1996; 271(40): 24655 - 24661. [Abstract] [Full Text] [PDF]
|
|
| 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 |
