Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P16104 (
H2AX
)
3,930
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We recently identified a novel human AlkB homologue,
ALKBH8
, which is expressed in various types of human cancers including human urothelial carcinomas. In examining the role and function of
ALKBH8
in human bladder cancer development in vitro, we found that silencing of
ALKBH8
through small interfering RNA transfection reduced reactive oxygen species (ROS) production via down-regulation of NAD(P)H oxidase-1 (NOX-1) and induced apoptosis through subsequent activation of c-jun NH(2)-terminal kinase (JNK) and p38. However, we also found that JNK and p38 activation resulted in phosphorylation of
H2AX
(gammaH2AX), a variant of mammalian histone H2A, which contributes to the apoptosis induced by silencing
ALKBH8
and NOX-1. Silencing of
ALKBH8
significantly suppressed invasion, angiogenesis, and growth of bladder cancers in vivo as assessed both in the chorioallantoic membrane assay and in an orthotopic mouse model using green fluorescent protein-labeled KU7 human urothelial carcinoma cells. Immunohistochemical examination showed high expression of
ALKBH8
and NOX-1 proteins in high-grade, superficially and deeply invasive carcinomas (pT(1) and >pT(2)) as well as in carcinoma in situ, but not in low-grade and noninvasive phenotypes (pT(a)). These findings indicate an essential role for
ALKBH8
in urothelial carcinoma cell survival mediated by NOX-1-dependent ROS signals, further suggesting new therapeutic strategies in human bladder cancer by inducing JNK/p38/gammaH2AX-mediated cell death by silencing of
ALKBH8
.
...
PMID:A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer progression. 1929 82
