SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2003-01-0157. This Article Full Text (PDF) All Versions of this Article: 2003-01-0157v1 102/5/1708    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sorensen, B. B Articles by Petersen, L. C Search for Related Content PubMed PubMed Citation Articles by Sorensen, B. B Articles by Petersen, L. C Social Bookmarking                   What's this? Submitted January 21, 2003 Accepted April 28, 2003 Anti-apoptotic effect of coagulation factor VIIa Brit B Sorensen*, L. Vijaya Mohan Rao, Ditte Tornehave, Steen Gammeltoft, and Lars C Petersen Hemostasis Biology, Novo Nordisk A/S, Maaloev, Denmark; Department of Clinical Biochemistry, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark Department of Biochemistry, University of Texas Health Center, Tyler, TX, USA Pharmacology Research, Novo Nordisk A/S, Bagsvaerd, Denmark Department of Clinical Biochemistry, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark Hemostasis Biology, Novo Nordisk A/S, Maaloev, Denmark * Corresponding author; email: bbsn{at}novonordisk.com. Binding of factor VIIa (FVIIa) to its cellular receptor tissue factor (TF) was previously shown to induce various intracellular signaling events, which were thought to be responsible for TF-mediated biological effects, including angiogenesis, tumor metastasis and restenosis. To understand the mechanisms behind these processes, we have examined the effect of FVIIa on apoptosis. Serum deprivation-induced apoptosis of BHK(+TF) cells was characterized by apoptotic blebs, nuclei with chromatin-condensed bodies, DNA degradation, and activation of caspase 3. FVIIa markedly decreased the number of cells with apoptotic morphology and prevented the DNA degradation as measured by means of TUNEL. The anti-apoptotic effect of FVIIa was confirmed by the observation that FVIIa attenuated caspase 3 activation. FVIIa-induced anti-apoptotic effect was dependent on its proteolytic activity and TF, but independent of factor Xa and thrombin. FVIIa-induced cell survival correlated with the activation of Akt and was inhibited markedly by the specific PI3-kinase inhibitor, LY294002. Blocking the activation of p44/42 MAPK by the specific MEK inhibitor, U0126, impaired modestly the ability of FVIIa to promote cell survival. In conclusion, FVIIa binding to TF provided protection against apoptosis induced by growth factor deprivation, primarily through activation of PI3-kinase/Akt pathway, and to a lesser extent, p44/42 MAPK pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Schaffner and W. Ruf Tissue Factor and PAR2 Signaling in the Tumor Microenvironment Arterioscler Thromb Vasc Biol, December 1, 2009; 29(12): 1999 - 2004. [Abstract] [Full Text] [PDF] H. H. Versteeg, F. Schaffner, M. Kerver, L. G. Ellies, P. Andrade-Gordon, B. M. Mueller, and W. Ruf Protease-Activated Receptor (PAR) 2, but not PAR1, Signaling Promotes the Development of Mammary Adenocarcinoma in Polyoma Middle T Mice Cancer Res., September 1, 2008; 68(17): 7219 - 7227. [Abstract] [Full Text] [PDF] H. H. Versteeg, F. Schaffner, M. Kerver, H. H. Petersen, J. Ahamed, B. Felding-Habermann, Y. Takada, B. M. Mueller, and W. Ruf Inhibition of tissue factor signaling suppresses tumor growth Blood, January 1, 2008; 111(1): 190 - 199. [Abstract] [Full Text] [PDF] Z. Salah, M. Maoz, E. Pokroy, M. Lotem, R. Bar-Shavit, and B. Uziely Protease-Activated Receptor-1 (hPar1), A Survival Factor Eliciting Tumor Progression Mol. Cancer Res., March 1, 2007; 5(3): 229 - 240. [Abstract] [Full Text] [PDF] S. Koizume, M.-S. Jin, E. Miyagi, F. Hirahara, Y. Nakamura, J.-H. Piao, A. Asai, A. Yoshida, E. Tsuchiya, W. Ruf, et al. Activation of Cancer Cell Migration and Invasion by Ectopic Synthesis of Coagulation Factor VII Cancer Res., October 1, 2006; 66(19): 9453 - 9460. [Abstract] [Full Text] [PDF] M. Belting, J. Ahamed, and W. Ruf Signaling of the Tissue Factor Coagulation Pathway in Angiogenesis and Cancer Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1545 - 1550. [Abstract] [Full Text] [PDF] S. Kato, M. Pinto, A. Carvajal, N. Espinoza, C. Monso, A. Sadarangani, M. Villalon, J. J. Brosens, J. O. White, J. K. Richer, et al. Progesterone Increases Tissue Factor Gene Expression, Procoagulant Activity, and Invasion in the Breast Cancer Cell Line ZR-75-1 J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1181 - 1188. [Abstract] [Full Text] [PDF] L. V. M. Rao and U. R. Pendurthi Tissue Factor-Factor VIIa Signaling Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 47 - 56. [Abstract] [Full Text] [PDF] H. H. Versteeg, C. A. Spek, S. H. Slofstra, S. H. Diks, D. J. Richel, and M. P. Peppelenbosch FVIIa:TF Induces Cell Survival via G12/G13-Dependent Jak/STAT Activation and BclXL Production Circ. Res., April 30, 2004; 94(8): 1032 - 1040. [Abstract] [Full Text] [PDF] G. M. Hjortoe, L. C. Petersen, T. Albrektsen, B. B. Sorensen, P. L. Norby, S. K. Mandal, U. R. Pendurthi, and L. V. M. Rao Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration Blood, April 15, 2004; 103(8): 3029 - 3037. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020