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: EC:3.4.22.62 (
caspase-9
)
7,507
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Deletion at chromosome 3p21.3 is the earliest and the most frequently observed genetic alteration in lung cancer, suggesting that the region contains tumor suppressor gene(s) (TSG). Identification of those genes may lead to the development both of biomarkers to identify high-risk individuals and novel therapeutics. Previously, we cloned the
H37
/Luca15/RBM5 gene from 3p21.3 and showed its TSG characteristics. To investigate the physiologic function of
H37
in the lung and its mechanism of tumor suppression, we have stably transfected
H37
into A549 non-small cell lung cancer cells. A549/
H37
cells show significant growth inhibition compared with the vector controls by in vitro and in vivo cell proliferation assays. Using this lung cancer cell model, we have found that the molecular mechanism of
H37
tumor suppression involves both cell cycle (G(1)) arrest and apoptosis. To further define
H37
's function in cell cycle/apoptotic pathways, we investigated differential expression profiles of various cell cycle and apoptosis regulatory proteins using Western blot analysis. Both cyclin A and phophorylated RB levels were decreased in
H37
-transfected cells, whereas expression of Bax protein was increased. Mitochondrial regulation of apoptosis further downstream of Bax was investigated, showing change in the mitochondrial membrane potential, cytochrome c release into the cytosol, and enhanced
caspase-9
and caspase-3 activities. We also report that
H37
may mediate apoptosis in a p53-independent manner, and Bax knockdown by small interfering RNA suggests Bax plays a functional role downstream of
H37
. Lastly, we proposed a tumor suppression model of
H37
as a post-transcriptional regulator for cell cycle/apoptotic-related proteins.
...
PMID:3p21.3 tumor suppressor gene H37/Luca15/RBM5 inhibits growth of human lung cancer cells through cell cycle arrest and apoptosis. 1658 63
