Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26985820
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2016 ; 11
(3
): e0151341
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute
Lymphoblastic Leukaemia Cells
#MMPMID26985820
Weeks RJ
; Ludgate JL
; LeMée G
; Morison IM
PLoS One
2016[]; 11
(3
): e0151341
PMID26985820
show ga
BACKGROUND: Childhood acute lymphoblastic leukaemia (ALL) is the most common
malignancy in children. Despite high cure rates, side effects and late
consequences of the intensive treatments are common. Unquestionably, the
identification of new therapeutic targets will lead to safer, more effective
treatments. We identified TES promoter methylation and transcriptional silencing
as a very common molecular abnormality in childhood ALL, irrespective of
molecular subtype. The aims of the present study were to demonstrate that TES
promoter methylation is aberrant, to determine the effects of TES re-expression
in ALL, and to determine if those effects are mediated via TP53 activity.
METHODS: Normal fetal and adult tissue DNA was isolated and TES promoter
methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot
were used to confirm re-expression of TES in ALL cell lines after
5'-aza-2'-deoxycytidine (decitabine) exposure or transfection with TES expression
plasmids. The effects of TES re-expression on ALL cells were investigated using
standard cell proliferation, cell death and cell cycle assays. RESULTS: In this
study, we confirm that the TES promoter is unmethylated in normal adult and fetal
tissues. We report that decitabine treatment of ALL cell lines results in
demethylation of the TES promoter and attendant expression of TES mRNA.
Re-expression of TESTIN protein in ALL cells using expression plasmid
transfection results in rapid cell death or cell cycle arrest independent of TP53
activity. CONCLUSIONS: These results suggest that TES is aberrantly methylated in
ALL and that re-expression of TESTIN has anti-leukaemia effects which point to
novel therapeutic opportunities for childhood ALL.