| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Biology and Genetics |
Friedrich Miescher Institute, CH-4002 Basel, Switzerland
MDA-MB-231 cells are highly metastatic breast tumor cells. Their high invasiveness is thought to be due to constitutively high levels of urokinase-type plasminogen activator (uPA) and its receptor. Previously (R. Nanbu et al., C. Eur. J. Biochem., 247: 169–174, 1997), we showed that uPA mRNA in these cells is stable and that mRNA degradation mediated by an AU-rich element (ARE) is impaired. Here we report that treatment of MDA-MB-231 cells with SB203580, an inhibitor of the stress-activated p38 mitogen-activated protein (MAP) kinase, strongly destabilized uPA mRNA in an ARE-dependent manner. In contrast, in LLC-PK1 and HeLa cells, uPA mRNA is unstable, and an ARE present in the 3' untranslated region plays a role in its degradation. Enhanced ARE-mediated mRNA destabilization induced by SB203580 was also observed in both LLC-PK1 and HeLa cells with a globin chimeric mRNA harboring two copies of the ARE (globin-2ARE) from uPA mRNA. Overexpression of constitutively active MKK6, a p38 upstream activator kinase, increased the stability of the globin-2ARE message in LLC-PK1 cells, confirming the participation of p38 in the regulation of ARE-mediated mRNA decay. Interestingly, the half-life of the uPA mRNA in the three cell lines studied correlated with the basal levels of active p38. SB203580 treatment of MDA-MB-231 cells decreased cell-associated uPA activity and dramatically reduced in vitro cell invasiveness. These results suggest the participation of p38 in the control of invasiveness through regulation of the stability of uPA and uPA receptor mRNA, which is also destabilized by p38.
This article has been cited by other articles:
|
|
 |
|
  K. Xu, C. M. Kitchen, H.-K. G. Shu, and T. J. Murphy Platelet-derived Growth Factor-induced Stabilization of Cyclooxygenase 2 mRNA in Rat Smooth Muscle Cells Requires the c-Src Family of Protein-tyrosine Kinases J. Biol. Chem., November 9, 2007; 282(45): 32699 - 32709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shetty, T. Velusamy, S. Idell, H. Tang, and P. K. Shetty Regulation of urokinase receptor expression by protein tyrosine phosphatases Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L414 - L421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Quemener, E. E. Gabison, B. Naimi, G. Lescaille, F. Bougatef, M. P. Podgorniak, G. Labarchede, C. Lebbe, F. Calvo, S. Menashi, et al. Extracellular Matrix Metalloproteinase Inducer Up-regulates the Urokinase-Type Plasminogen Activator System Promoting Tumor Cell Invasion Cancer Res., January 1, 2007; 67(1): 9 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fawal, F. Armstrong, S. Ollier, H. Dupont, C. Touriol, B. Monsarrat, G. Delsol, B. Payrastre, and D. Morello A "liaison dangereuse" between AUF1/hnRNPD and the oncogenic tyrosine kinase NPM-ALK Blood, October 15, 2006; 108(8): 2780 - 2788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. G. Harper, S. M. Alvares, and W. G. Carter Wounding activates p38 map kinase and activation transcription factor 3 in leading keratinocytes J. Cell Sci., August 1, 2005; 118(15): 3471 - 3485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Iyer, K. Pumiglia, and C. M. DiPersio {alpha}3{beta}1 integrin regulates MMP-9 mRNA stability in immortalized keratinocytes: a novel mechanism of integrin-mediated MMP gene expression J. Cell Sci., March 15, 2005; 118(6): 1185 - 1195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Gauthier, C. R. Pickering, C. J. Miller, C. A. Fordyce, K. L. Chew, H. K. Berman, and T. D. Tlsty p38 Regulates Cyclooxygenase-2 in Human Mammary Epithelial Cells and Is Activated in Premalignant Tissue Cancer Res., March 1, 2005; 65(5): 1792 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yu, D. Bian, C. Mahanivong, R. K. Cheng, W. Zhou, and S. Huang p38 Mitogen-activated Protein Kinase Regulation of Endothelial Cell Migration Depends on Urokinase Plasminogen Activator Expression J. Biol. Chem., November 26, 2004; 279(48): 50446 - 50454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Lin, D. K. Crockett, S. D. Jenson, M. S. Lim, and K. S. J. Elenitoba-Johnson Quantitative Proteomic and Transcriptional Analysis of the Response to the p38 Mitogen-activated Protein Kinase Inhibitor SB203580 in Transformed Follicular Lymphoma Cells Mol. Cell. Proteomics, August 1, 2004; 3(8): 820 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Cook, H. E. Mischo, and J. A. Steitz The Herpesvirus saimiri Small Nuclear RNAs Recruit AU-Rich Element-Binding Proteins but Do Not Alter Host AU-Rich Element-Containing mRNA Levels in Virally Transformed T Cells Mol. Cell. Biol., May 15, 2004; 24(10): 4522 - 4533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shetty and S. Idell Urokinase Receptor mRNA Stability Involves Tyrosine Phosphorylation in Lung Epithelial Cells Am. J. Respir. Cell Mol. Biol., January 1, 2004; 30(1): 69 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tran, F. Maurer, and Y. Nagamine Stabilization of Urokinase and Urokinase Receptor mRNAs by HuR Is Linked to Its Cytoplasmic Accumulation Induced by Activated Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Mol. Cell. Biol., October 15, 2003; 23(20): 7177 - 7188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Wilson, J. Lu, K. Sutphen, Y. Sun, Y. Huynh, and G. Brewer Regulation of A + U-rich Element-directed mRNA Turnover Involving Reversible Phosphorylation of AUF1 J. Biol. Chem., August 29, 2003; 278(35): 33029 - 33038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Essig and G. Friedlander Tubular Shear Stress and Phenotype of Renal Proximal Tubular Cells J. Am. Soc. Nephrol., June 1, 2003; 14(90001): S33 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. E. Frevel, T. Bakheet, A. M. Silva, J. G. Hissong, K. S. A. Khabar, and B. R. G. Williams p38 Mitogen-Activated Protein Kinase-Dependent and -Independent Signaling of mRNA Stability of AU-Rich Element-Containing Transcripts Mol. Cell. Biol., January 15, 2003; 23(2): 425 - 436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Han, J. Leng, D. Bian, C. Mahanivong, K. A. Carpenter, Z. K. Pan, J. Han, and S. Huang Rac1-MKK3-p38-MAPKAPK2 Pathway Promotes Urokinase Plasminogen Activator mRNA Stability in Invasive Breast Cancer Cells J. Biol. Chem., December 6, 2002; 277(50): 48379 - 48385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Ibanez-Tallon, C. Ferrai, E. Longobardi, I. Facetti, F. Blasi, and M. P. Crippa Binding of Sp1 to the proximal promoter links constitutive expression of the human uPA gene and invasive potential of PC3 cells Blood, October 16, 2002; 100(9): 3325 - 3332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. S. Butler, M. M. Monick, T. O. Yarovinsky, L. S. Powers, and G. W. Hunninghake Altered IL-4 mRNA Stability Correlates with Th1 and Th2 Bias and Susceptibility to Hypersensitivity Pneumonitis in Two Inbred Strains of Mice J. Immunol., October 1, 2002; 169(7): 3700 - 3709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hata, A. Andoh, M. Shimada, S. Fujino, S. Bamba, Y. Araki, T. Okuno, Y. Fujiyama, and T. Bamba IL-17 stimulates inflammatory responses via NF-kappa B and MAP kinase pathways in human colonic myofibroblasts Am J Physiol Gastrointest Liver Physiol, June 1, 2002; 282(6): G1035 - G1044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Essig, F. Terzi, M. Burtin, and G. Friedlander Mechanical strains induced by tubular flow affect the phenotype of proximal tubular cells Am J Physiol Renal Physiol, October 1, 2001; 281(4): F751 - F762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Tacchini, P. Dansi, E. Matteucci, and M. A. Desiderio Hepatocyte growth factor signalling stimulates hypoxia inducible factor-1 (HIF-1) activity in HepG2 hepatoma cells Carcinogenesis, September 1, 2001; 22(9): 1363 - 1371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Aguirre-Ghiso, D. Liu, A. Mignatti, K. Kovalski, and L. Ossowski Urokinase Receptor and Fibronectin Regulate the ERKMAPK to p38MAPK Activity Ratios That Determine Carcinoma Cell Proliferation or Dormancy In Vivo Mol. Biol. Cell, April 1, 2001; 12(4): 863 - 879. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. Bakheet, M. Frevel, B. R. G. Williams, W. Greer, and K. S. A. Khabar ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins Nucleic Acids Res., January 1, 2001; 29(1): 246 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-C. Jang, T. Sanchez, H.-J. Schaefers, O. C. Trifan, C. H. Liu, C. Creminon, C.-K. Huang, and T. Hla Serum Withdrawal-induced Post-transcriptional Stabilization of Cyclooxygenase-2 mRNA in MDA-MB-231 Mammary Carcinoma Cells Requires the Activity of the p38 Stress-activated Protein Kinase J. Biol. Chem., December 8, 2000; 275(50): 39507 - 39515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-O. Yoon, M.-M. Kim, and A.-S. Chung Inhibitory Effect of Selenite on Invasion of HT1080 Tumor Cells J. Biol. Chem., June 1, 2001; 276(23): 20085 - 20092. [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 |
