Immortalization of human lymphocytes by co-cultivation with lethally irradiated autologous T-cell lines harbouring human T-cell leukaemia virus-I

1985 ◽  
Vol 110 (1) ◽  
pp. 82-84 ◽  
Author(s):  
T. Akagi ◽  
Y. Ohtsuki ◽  
K. Takahashi ◽  
I. Takeda ◽  
T. Oka ◽  
...  
2007 ◽  
Vol 406 (2) ◽  
pp. 317-323 ◽  
Author(s):  
Mariko Tomita ◽  
Gregg L. Semenza ◽  
Canine Michiels ◽  
Takehiro Matsuda ◽  
Jun-Nosuke Uchihara ◽  
...  

HTLV-1 (human T-cell leukaemia virus type 1) is the causative agent for ATL (adult T-cell leukaemia). HTLV-1 Tax can activate the PI3K (phosphoinositide 3-kinase)/Akt signalling pathway, which is responsible for survival of HTLV-1-infected T-cells. HIFs (hypoxia-inducible factors) are transcriptional regulators that play a central role in the response to hypoxia. Overexpression of HIF-1α in many cancers is associated with a poor response to treatment and increased patient mortality. Our objectives in the present study were to investigate whether HIF-1 was activated in HTLV-1-infected T-cells and to elucidate the molecular mechanisms of HIF-1 activation by focusing on the PI3K/Akt signalling pathway. We detected a potent pathway that activated HIF-1 in the HTLV-1-infected T-cells under a normal oxygen concentration. Enhanced HIF-1α protein expression and HIF-1 DNA-binding activity were exhibited in HTLV-1-infected T-cell lines. Knockdown of HIF-1α by siRNA (small interfering RNA) suppressed the growth and VEGF (vascular endothelial growth factor) expression of the HTLV-1-infected T-cell line. HIF-1 protein accumulation and transcriptional activity were enhanced by Tax, which was inhibited by dominant-negative Akt. Importantly, mutant forms of Tax that are defective in activation of the PI3K/Akt pathway failed to induce HIF-1 transcriptional activity. The PI3K inhibitor LY294002 suppressed HIF-1α protein expression, HIF-1 DNA-binding and HIF-1 transcriptional activity in HTLV-1-infected T-cell lines. In primary ATL cells, HIF-1α protein levels were strongly correlated with levels of phosphorylated Akt. The results of the present study suggest that PI3K/Akt activation induced by Tax leads to activation of HIF-1. As HIF-1 plays a major role in tumour progression, it may represent a molecular target for the development of novel ATL therapeutics.


1998 ◽  
Vol 103 (3) ◽  
pp. 721-728 ◽  
Author(s):  
Kenji Ishitsuka ◽  
Shuichi Hanada ◽  
Shinsuke Suzuki ◽  
Atae Utsunomiya ◽  
Yoshiko Chyuman ◽  
...  

1985 ◽  
Vol 51 (6) ◽  
pp. 753-759 ◽  
Author(s):  
S Hinuma ◽  
S Honda ◽  
K Tsukamoto ◽  
K Sugamura ◽  
Y Hinuma

1994 ◽  
Vol 50 (1-3) ◽  
pp. 219-225 ◽  
Author(s):  
Karen F.T. Copeland ◽  
Anthonius G.M. Haaksma ◽  
David Derse ◽  
Jonathan L. Heeney

2011 ◽  
Vol 434 (3) ◽  
pp. 571-571 ◽  
Author(s):  
M. Tomita ◽  
G. L. Semenza ◽  
C. Michiels ◽  
T. Matsuda ◽  
J.-N. Uchihara ◽  
...  

1992 ◽  
Vol 66 (11) ◽  
pp. 6788-6793 ◽  
Author(s):  
D Ou ◽  
P Chong ◽  
Y Choi ◽  
P McVeigh ◽  
W A Jefferies ◽  
...  

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