|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 31, 29226-29232, August 3, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Nephrology, Istituto G. Gaslini, Largo G. Gaslini, 5, 16147 Genova, Italy, the Several investigations have suggested a putative
tumor suppressor role for lysyl oxidase because it is down-regulated in
many human and oncogene-induced tumors. To address this issue we
down-regulated the enzyme in normal rat kidney fibroblasts by stable
transfection of its cDNA in an antisense orientation. The selected
clones revealed an absence of lysyl oxidase and dramatic phenotypic
changes, interpretable as signs of transformation. The antisense lysyl
oxidase clones showed, indeed, loose attachment to the plate and
anchorage-independent growth and were highly tumorigenic in nude mice.
Moreover, we found an impaired response of the PDGF and IGF-1 receptors
to their ligands. In particular, the transformed cells showed a
down-regulation of both PDGF receptors and expressed the 105-kDa
isoform of the IGF-1
Down-regulation of Lysyl Oxidase-induced Tumorigenic
Transformation in NRK-49F Cells Characterized by Constitutive
Activation of Ras Proto-oncogene*
, Istituto Nazionale
per la Ricerca sul Cancro, 16136 Genova, Italy, and the
§ Institute de Biologie et Chimie des Protéines, UPR
412-CNRS, 69367 Lyon, France
receptor, which was not present in the normal
control cells. The lack of response to PDGF-BB has been described as a
feature of many ras-transformed phenotypes. Therefore, we
looked at the status of the p21ras.
Indeed, we found a significantly higher level of active
p21ras both during steady-state growth and
prolonged starvation. Our data reveal new evidence for a tumor
suppressor activity of lysyl oxidase, highlighting its particular role
in controlling Ras activation and growth factor dependence.
*
This work was supported by The Italian Ministry of
Scientific Research, the French Center National de la Recherche
Scientifique, and by the French Association de la Recherche pour le
Cancer.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Wu, C. Min, X. Wang, Z. Yu, K. H. Kirsch, P. C. Trackman, and G. E. Sonenshein Repression of BCL2 by the Tumor Suppressor Activity of the Lysyl Oxidase Propeptide Inhibits Transformed Phenotype of Lung and Pancreatic Cancer Cells Cancer Res., July 1, 2007; 67(13): 6278 - 6285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wu, Z. Guo, X. Chang, M. S. Kim, J. K. Nagpal, J. Liu, J. M. Maki, K. I. Kivirikko, S. P. Ethier, B. Trink, et al. LOXL1 and LOXL4 Are Epigenetically Silenced and Can Inhibit Ras/Extracellular Signal-Regulated Kinase Signaling Pathway in Human Bladder Cancer Cancer Res., May 1, 2007; 67(9): 4123 - 4129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Min, K. H. Kirsch, Y. Zhao, S. Jeay, A. H. Palamakumbura, P. C. Trackman, and G. E. Sonenshein The Tumor Suppressor Activity of the Lysyl Oxidase Propeptide Reverses the Invasive Phenotype of Her-2/neu-Driven Breast Cancer Cancer Res., February 1, 2007; 67(3): 1105 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-E. Lee and Y. Kim A Tissue-specific Variant of the Human Lysyl Oxidase-like Protein 3 (LOXL3) Functions as an Amine Oxidase with Substrate Specificity J. Biol. Chem., December 8, 2006; 281(49): 37282 - 37290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bouez, C. Reynaud, E. Noblesse, A. Thepot, C. Gleyzal, J. Kanitakis, E. Perrier, O. Damour, and P. Sommer The Lysyl Oxidase LOX Is Absent in Basal and Squamous Cell Carcinomas and Its Knockdown Induces an Invading Phenotype in a Skin Equivalent Model Clin. Cancer Res., March 1, 2006; 12(5): 1463 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Palamakumbura, S. Jeay, Y. Guo, N. Pischon, P. Sommer, G. E. Sonenshein, and P. C. Trackman The Propeptide Domain of Lysyl Oxidase Induces Phenotypic Reversion of Ras-transformed Cells J. Biol. Chem., September 24, 2004; 279(39): 40593 - 40600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Palamakumbura, P. Sommer, and P. C. Trackman Autocrine Growth Factor Regulation of Lysyl Oxidase Expression in Transformed Fibroblasts J. Biol. Chem., August 15, 2003; 278(33): 30781 - 30787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jeay, S. Pianetti, H. M. Kagan, and G. E. Sonenshein Lysyl Oxidase Inhibits Ras-Mediated Transformation by Preventing Activation of NF-{kappa}B Mol. Cell. Biol., April 1, 2003; 23(7): 2251 - 2263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Kirschmann, E. A. Seftor, S. F. T. Fong, D. R. C. Nieva, C. M. Sullivan, E. M. Edwards, P. Sommer, K. Csiszar, and M. J. C. Hendrix A Molecular Role for Lysyl Oxidase in Breast Cancer Invasion Cancer Res., August 1, 2002; 62(15): 4478 - 4483. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |