Inhibition of phosphatidylinositol 3'-kinase induces preferentially killing of PTEN-null T leukemias through AKT pathway

Biochemical and Biophysical Research Communications
S UddinKishor G Bhatia

Abstract

We examined the functional role of the phosphatidylinositol 3'-kinase pathway in the growth and survival of cell lines of T-cell origin. Pharmacological inhibition of PI3'-kinase using LY294002 resulted in apoptosis of acute lymphoblastic T-cell leukemia (T-ALL) cell lines including CEM, Jurkat, and MOLT-4. On the other hand, the cutaneous T-cell lymphoma cell line HUT-78 was found to be refractory to LY294002- inducible apoptosis. Sensitivity or resistance to pharmacological inhibitors of PI3'-kinase correlated with tumor suppressor PTEN gene expression, as sensitive T-ALL cells do not express PTEN and have high level of activated AKT, in contrast to HUT-78 cells. Our data demonstrate that inhibition of PI3'-kinase results in dephosphorylation of AKT and partial inhibition of Bcl-xL expression in T-ALL cells, but not in HUT-78 cells. Interestingly, HUT-78 cells were also found to express higher levels of Bcl-xL protein as compared to T-ALL cells. Inhibition of PI3'-kinase also induces release of cytochrome c from mitochondria and activation of caspase-3 and PARP in all T-ALL cell lines tested, but not in HUT-78 cells. Taken altogether, our data demonstrate that the PI3'-kinase/AKT pathway plays a major role in the growth and s...Continue Reading

References

Feb 21, 1997·Cell·T F FrankeL C Cantley
Aug 11, 1998·Nature Genetics·A Di CristofanoP P Pandolfi
Nov 13, 1998·Science·M H CardoneJ C Reed
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·X WuC L Sawyers
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·K PodsypaninaR Parsons
Apr 3, 1999·British Journal of Cancer·M P DaviesC Walker
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·L C Cantley, B G Neel
Sep 15, 1999·Nature·J A Romashkova, S S Makarov
Feb 29, 2000·Cell·A Di Cristofano, P P Pandolfi
Jan 16, 2002·Current Opinion in Genetics & Development·Charles L Sawyers
Feb 13, 2002·The Journal of Biological Chemistry·Shahab UddinLeonidas C Platanias
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robin W FreeburnStephen G Ward
Dec 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Shahab UddinAmittha Wickrema

❮ Previous
Next ❯

Citations

Feb 28, 2006·Apoptosis : an International Journal on Programmed Cell Death·A R HussainS Uddin
Oct 6, 2007·Immunologic Research·Masaki KashiwadaPaul B Rothman
Mar 23, 2005·Current Opinion in Cell Biology·Matthias P Wymann, Romina Marone
Aug 25, 2011·The Journal of Biological Chemistry·Jing ChengLawrence P Kane
Jul 16, 2005·Leukemia & Lymphoma·Joao T BarataVassiliki A Boussiotis
Aug 12, 2008·British Journal of Haematology·Pieter Van VlierbergheJules P P Meijerink
Aug 13, 2008·Expert Opinion on Therapeutic Targets·Linda S SteelmanJames A McCubrey
May 20, 2008·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·B A CardosoJ T Barata
Jun 10, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Shahab UddinKhawla S Al-Kuraya
Sep 13, 2007·Journal of Cellular Biochemistry·Elisabetta CalzavaraPaola Comi
Mar 10, 2006·Journal of Cellular Physiology·Irina MantovaniAlberto M Martelli
Jun 9, 2015·Genes, Chromosomes & Cancer·Natalia PlatonovaRaffaella Chiaramonte
Apr 19, 2007·Cancer Research·Azhar R HussainShahab Uddin
Apr 20, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shahab UddinKishor G Bhatia
Apr 17, 2007·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yun ZhangXiaoxiang Zheng

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis