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Query: UMLS:C0001486 (
Adenovirus
)
3,125
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
BMP-2
(bone morphogenetic protein-2) promotes differentiation of osteoblast precursor cells to mature osteoblasts that form healthy bone. In the present study, we demonstrate a novel mechanism of
BMP-2
-induced osteoblast differentiation. The antioxidant NAC (N-acetyl-L-cysteine) and the flavoprotein enzyme NAD(P)H oxidase inhibitor DPI (diphenyleneiodonium) prevented
BMP-2
-stimulated alkaline phosphatase expression and mineralized bone nodule formation in mouse 2T3 pre-osteoblasts.
BMP-2
elicited a rapid generation of ROS (reactive oxygen species) concomitant with increased activation of NAD(P)H oxidase. NAC and DPI inhibited
BMP-2
-induced ROS production and NAD(P)H oxidase activity respectively. NAD(P)H oxidases display structurally similar catalytic subunits (Nox1-5) with differential expression in various cells. We demonstrate that 2T3 pre-osteoblasts predominantly express the Nox4 isotype of NAD(P)H oxidase. To extend this finding, we tested the functional effects of Nox4.
Adenovirus
-mediated expression of dominant-negative Nox4 inhibited
BMP-2
-induced alkaline phosphatase expression.
BMP-2
promotes expression of
BMP-2
for maintenance of the osteoblast phenotype. NAC and DPI significantly blocked
BMP-2
-stimulated expression of BMP2 mRNA and protein due to a decrease in BMP2 gene transcription. Dominant-negative Nox4 also mimicked this effect of NAC and DPI. Our results provide the first evidence for a new signalling pathway linking
BMP-2
-stimulated Nox4-derived physiological ROS to
BMP-2
expression and osteoblast differentiation.
...
PMID:Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation. 2102 48
Bone morphogenetic protein 2
(
BMP-2
) is a member of the TGF-beta superfamily of signaling molecules, and has been shown to function as a tumor suppressor involved in development and progression of many malignancies.
BMP-2
has previously been reported to be closely correlated with lung cancer. But, the role and molecular mechanisms of
BMP-2
in lung cancer have not yet been comprehensively explained. The present study aims to elucidate the role of
BMP-2
in growth and invasion of human lung adenocarcinoma (LAC) in vitro and in vivo.
Adenovirus
vector-mediated
BMP-2
small hairpin RNA (shBMP-2) was used to transfect into A549 LAC cells to determine the functional relevance of
BMP-2
and tumor growth and invasion in vitro and in vivo, and further investigate the expression levels of
BMP-2
, vascular endothelial growth factor (VEGF), matrix metallopeptidase-9 (MMP-9), phosphatidylinositol 3-kinase p85alpha (PI3Kp85alpha) and phosphorylated AKT (p-AKT). As a result, LAC cell proliferation and invasion were significantly diminished by knockdown of
BMP-2
indicated by MTT and Transwell assays, and cell apoptosis and cycle arrest were markedly induced indicated by flow cytometry. When
BMP-2
expression was knocked down, the expression of PI3Kp85alpha, p-AKT, VEGF and MMP-9 was also down-regulated in LAC cells. In addition, the tumor volumes in LAC subcutaneous nude mouse model treated with shBMP-2 were significantly smaller than those in control and ad-GFP groups. Taken together, our findings indicate that knockdown of
BMP-2
inhibits growth and invasion of LAC cells possibly via blockade of the PI3K/AKT signaling pathway, and
BMP-2
may be a potential therapeutic target for lung cancer.
...
PMID:Adenovirus mediated knockdown of bone morphogenetic protein 2 inhibits human lung cancer growth and invasion in vitro and in vivo. 2329 87
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