|
|
Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2003-01-0157.
 Previous Article | Table of Contents | Next Article 
Blood, 1 September 2003, Vol. 102, No. 5, pp. 1708-1715
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Antiapoptotic effect of coagulation factor VIIa
Brit B. Sorensen,
L. Vijaya Mohan Rao,
Ditte Tornehave,
Steen Gammeltoft, and
Lars C. Petersen
From Hemostasis Biology, Novo Nordisk, Maaloev, Denmark; the Department
of Biochemistry, University of Texas Health Center at Tyler, TX; Pharmacology
Research, Novo Nordisk, Bagsvaerd, Denmark; and the Department of Clinical
Biochemistry, Glostrup Hospital, University of Copenhagen, Glostrup,
Denmark.
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 biologic 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
TdT-mediated dUTP nick end labeling (TUNEL). The antiapoptotic effect of FVIIa
was confirmed by the observation that FVIIa attenuated caspase 3 activation.
FVIIa-induced antiapoptotic 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
mitogen-activated protein kinase (MAPK) by the specific mitogen-induced
extracellular kinase (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:
|
|
|
|
 
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]
|
|
|
|
|
