Nucleic Acids Research, 1995, Vol. 23, No. 19 3887-3893
© 1995
MOLECULAR BIOLOGY |
Inhibition of NF-KB-Rel A expression by antisense oligodeoxynucleotides suppresses synthesis of urokinase-type plasminogen activator (uPA) but not its inhibitor PAl-1
Frauenklinik der Technischen Universität München Klinikum rechts der lsar, D-81675 München, Germany 3Hamamastu University, School of Medicine Hamamatsu, Japan 1University of Milan, Department of Genetics and Microbiology Milan, Italy 2DIBIT, San Raffaele Hospital Milan, Italy
*To whom correspondence should be addressed
Received July 4, 1995. Revised September 1, 1995. Accepted September 1, 1995.
The essential role of uroklnase-type plasminogen activator (uPA) in tumor invasion and metastasis stresses the necessity of a fine-tuned cellular control over its expression. It has been shown that changes in uPA directly correlate with changes in cell invasive ness. We examined the role of Rel-related proteins in uPA synthesis by human ovarian cancer cells by inhibiting their expression using the antisense (AS) oligodeoxynucleotide (ODN) technology. Exposure of OV-MZ-6 cells to 10µM phosphorothioate (PS)-dervatized AS-ODN directed to Rel A led to a maximal 50% decrease of uPA antigen in cell lysates and a 70% reduction in cell culture supematants accompanied by a significant transient decline in uPA mRNA levels. Antisense-PS-ODN directed to NF-kB1 (p50) or c-rel had no effect on uPA protein expression. AS-PS-ODN directed to Rel A also affected the proteotytic capacity of OV-MZ-6 cells reflected by an -70% decrease in the tibrinolytic capacity of the cells within 24 h compared to untreated controls. AS-PS-ODN directed to 1kB
expression increased uPA in cell culture supematants up to 50%. uPA receptor (uPAR) production and synthesis of plasminogen activator inhibitor type-1 (PM-1) were not altered by either AS-PS-ODN applied. Western blot and gel retardation analyses revealed constitutive expression of Relrelated proteins in nuclear protein extracts of OV-MZ-6 cells. Thus these proteins seem to be implicated in uPA regulation and may thereby contribute to tumor spread and metastasis.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Kobayashi, T. Yagyu, T. Kondo, N. Kurita, K. Inagaki, S. Haruta, R. Kawaguchi, T. Kitanaka, Y. Sakamoto, Y. Yamada, et al. Suppression of Urokinase Receptor Expression by Thalidomide Is Associated with Inhibition of Nuclear Factor {kappa}B Activation and Subsequently Suppressed Ovarian Cancer Dissemination Cancer Res., November 15, 2005; 65(22): 10464 - 10471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sasaki, T. Morisaki, K. Hashizume, T. Yao, M. Tsuneyoshi, H. Noshiro, K. Nakamura, T. Yamanaka, A. Uchiyama, M. Tanaka, et al. Nuclear Factor-{kappa}B p65 (RelA) Transcription Factor Is Constitutively Activated in Human Gastric Carcinoma Tissue Clin. Cancer Res., December 1, 2001; 7(12): 4136 - 4142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kroon, P Koolwijk, B van der Vecht, and V. van Hinsbergh Hypoxia in combination with FGF-2 induces tube formation by human microvascular endothelial cells in a fibrin matrix: involvement of at least two signal transduction pathways J. Cell Sci., January 2, 2001; 114(4): 825 - 833. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Kojima, S. Hayashi, K. Shimokado, Y. Suzuki, J. Shimada, M. P. Crippa, and S. L. Friedman Transcriptional activation of urokinase by the Kruppel-like factor Zf9/COPEB activates latent TGF-beta 1 in vascular endothelial cells Blood, February 15, 2000; 95(4): 1309 - 1316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Komine, L. S. Rao, T. Kaneko, M. Tomic-Canic, K. Tamaki, I. M. Freedberg, and M. Blumenberg Inflammatory Versus Proliferative Processes in Epidermis. TUMOR NECROSIS FACTOR alpha INDUCES K6b KERATIN SYNTHESIS THROUGH A TRANSCRIPTIONAL COMPLEX CONTAINING NFkappa B AND C/EBPbeta J. Biol. Chem., October 6, 2000; 275(41): 32077 - 32088. [Abstract] [Full Text] [PDF]
|
|