Inhibitor of growth 4 induces growth suppression and apoptosis in glioma U87MG.
OBJECTIVE
Inhibitor of growth (ING) 4 is a member of the ING family proteins. It has been shown to play an important role in cell cycle, transcription and oncogenesis, but the molecular mechanism of ING4 on tumor growth inhibition has not yet been elucidated. The goal of this study is to investigate the inhibitory effects of ING4 on gliomas and its mechanism by transduction of ING4 cDNA into glioma U87MG.


METHODS
The effect and mechanisms of ING4 on proliferation and apoptosis of U87MG were evaluated in vitro by MTT assay, flow-cytometric analysis, TUNEL assay, Western blot analysis and animal experiments.


RESULTS
The level of ING4 was markedly reduced in glioma tissues, and the extent of reduction correlated with the progression from lower to higher grades of tumors. It was observed that U87MG with exogenous ING4 gene presented with growth suppression, apoptosis enhancement and the deregulation of cell cycle- or apoptosis-regulating proteins.


CONCLUSIONS
ING4 has a potential role on the growth suppression and apoptosis enhancement in gliomas U87MG via the activation of mitochondrial-induced apoptotic pathway and the hindrance of the cell cycle progression. The low expression and dysfunction of ING4 might be correlated with the tumorigenesis and progression of gliomas.
Li
Xiaomei
X
Department of Pathology, Harbin Medical University, China.
Cai
Limin
L
Chen
Hui
H
Zhang
Qingyuan
Q
Zhang
Shujun
S
Wang
Yanhua
Y
Dong
Yanyan
Y
Cheng
Hui
H
Qi
Jiping
J
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D017931:DNA Primers; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins